The document summarizes a presentation on drug discovery and development processes, specifically focusing on the potential for prodrug strategies to increase success rates. It discusses how drugs are discovered and developed, including identifying drug targets and conducting preclinical and clinical trials. It then explains what prodrugs are, how they can help address issues like low bioavailability and metabolism, and provide strategies to increase solubility, permeability, bioavailability and drug half-life. The presentation aims to illustrate how prodrug design may help overcome barriers in drug development and increase the success of bringing new drugs to market.
This document discusses bioavailability and methods to enhance it. It defines bioavailability as the rate and extent of drug absorption from its dosage form. Bioavailability can be measured using pharmacokinetic or pharmacodynamic methods. Pharmacokinetic methods measure parameters from plasma concentration-time curves like Cmax, Tmax, and AUC. These provide information on absorption rate and extent. Urinary excretion studies also quantify bioavailability. Methods to enhance bioavailability include increasing drug solubility through techniques like micronization, improving membrane permeability using lipid formulations, and stabilizing drugs with coatings. The objectives of bioavailability studies are drug development, comparing formulations, and evaluating absorption between dosage forms.
Antiviral agents history, classification,mechanism of action and adverse effectMuhammad Amir Sohail
Viruses consist of a nucleic acid core surrounded by a protein capsid. Some viruses have an outer envelope. There are several stages to viral replication within a host cell, including attachment, entry, uncoating, transcription/translation, replication, assembly and release. Antiviral drugs target different stages of the viral life cycle and can be classified as inhibitors of attachment/entry, nucleic acid synthesis, uncoating/assembly, or immunomodulators. Examples of antivirals for influenza include neuraminidase inhibitors which prevent release and amantadine/rimantadine which inhibit uncoating. Ribavirin is used for RSV. Interferons, lamivudine and entecav
Basic Concepts & Application of Prodrugs Design [Antiviral,Antibiotics,GPAT Q...ThePharmaFacts
PCI Syllabus 6th Semester Medicinal Chemistry III
Introduction
History of Prodrug
Prodrug Concept
Classification of Prodrug
Objectives of Prodrug
Applications of Prodrug
Q&A on Prodrug
Protein binding of drugs can be reversible or irreversible. Reversible binding involves weak interactions like hydrogen bonds or hydrophobic bonds, while irreversible binding results from covalent bonds. Drugs bind to plasma proteins like albumin and alpha-1-acid glycoprotein, as well as to components in blood cells and extravascular tissues. The extent of protein binding affects the absorption, distribution, metabolism, and excretion of drugs. It determines the amount of active, unbound drug available to elicit its pharmacological response. Protein binding is influenced by factors related to the drug, binding proteins, and patient characteristics. It is important for understanding a drug's pharmacokinetics and pharmacodynamics.
Methods of enhancing bioavailability of drugsDebasish Ghadei
This document discusses various approaches to enhancing the bioavailability of drugs, including enhancing drug solubility, permeability, stability, and gastrointestinal retention. It describes how bioavailability can be improved by increasing a drug's dissolution rate through methods like micronization, nanosuspensions, and use of surfactants. Permeability can be enhanced using lipid technologies, ion pairing, or penetration enhancers. Stability can be improved with enteric coatings or complexation. Gastrointestinal retention time can be lengthened to boost absorption.
The document discusses the concept of prodrugs. It defines prodrugs as therapeutically inactive compounds that are metabolized into active drug metabolites. The objectives of prodrug design are to overcome barriers like poor solubility, stability, absorption and toxicity. An ideal prodrug is pharmacologically inert, transforms rapidly into the active form at the target site, and produces non-toxic metabolic fragments. Prodrugs are classified based on their structure and site of conversion. The applications of prodrugs include improving drug properties and delivery.
This document provides information on renal excretion of drugs. It discusses how the kidney is the primary route of elimination for water soluble, non-volatile and small molecule drugs. The basic functional unit of the kidney is the nephron, which filters drugs from the blood and reabsorbs or secretes them via processes like glomerular filtration, tubular secretion and reabsorption. Factors that influence renal excretion include the physicochemical properties of drugs as well as physiological and pathological factors. Renal impairment decreases drug clearance leading to prolonged drug exposure. Methods to assess renal function and adjust drug dosing based on renal function are also described.
factors affecting protein drug binding
significance of protein binding
drug related factors
protein related factors
drug interactions
patient related factors
This document discusses bioavailability and methods to enhance it. It defines bioavailability as the rate and extent of drug absorption from its dosage form. Bioavailability can be measured using pharmacokinetic or pharmacodynamic methods. Pharmacokinetic methods measure parameters from plasma concentration-time curves like Cmax, Tmax, and AUC. These provide information on absorption rate and extent. Urinary excretion studies also quantify bioavailability. Methods to enhance bioavailability include increasing drug solubility through techniques like micronization, improving membrane permeability using lipid formulations, and stabilizing drugs with coatings. The objectives of bioavailability studies are drug development, comparing formulations, and evaluating absorption between dosage forms.
Antiviral agents history, classification,mechanism of action and adverse effectMuhammad Amir Sohail
Viruses consist of a nucleic acid core surrounded by a protein capsid. Some viruses have an outer envelope. There are several stages to viral replication within a host cell, including attachment, entry, uncoating, transcription/translation, replication, assembly and release. Antiviral drugs target different stages of the viral life cycle and can be classified as inhibitors of attachment/entry, nucleic acid synthesis, uncoating/assembly, or immunomodulators. Examples of antivirals for influenza include neuraminidase inhibitors which prevent release and amantadine/rimantadine which inhibit uncoating. Ribavirin is used for RSV. Interferons, lamivudine and entecav
Basic Concepts & Application of Prodrugs Design [Antiviral,Antibiotics,GPAT Q...ThePharmaFacts
PCI Syllabus 6th Semester Medicinal Chemistry III
Introduction
History of Prodrug
Prodrug Concept
Classification of Prodrug
Objectives of Prodrug
Applications of Prodrug
Q&A on Prodrug
Protein binding of drugs can be reversible or irreversible. Reversible binding involves weak interactions like hydrogen bonds or hydrophobic bonds, while irreversible binding results from covalent bonds. Drugs bind to plasma proteins like albumin and alpha-1-acid glycoprotein, as well as to components in blood cells and extravascular tissues. The extent of protein binding affects the absorption, distribution, metabolism, and excretion of drugs. It determines the amount of active, unbound drug available to elicit its pharmacological response. Protein binding is influenced by factors related to the drug, binding proteins, and patient characteristics. It is important for understanding a drug's pharmacokinetics and pharmacodynamics.
Methods of enhancing bioavailability of drugsDebasish Ghadei
This document discusses various approaches to enhancing the bioavailability of drugs, including enhancing drug solubility, permeability, stability, and gastrointestinal retention. It describes how bioavailability can be improved by increasing a drug's dissolution rate through methods like micronization, nanosuspensions, and use of surfactants. Permeability can be enhanced using lipid technologies, ion pairing, or penetration enhancers. Stability can be improved with enteric coatings or complexation. Gastrointestinal retention time can be lengthened to boost absorption.
The document discusses the concept of prodrugs. It defines prodrugs as therapeutically inactive compounds that are metabolized into active drug metabolites. The objectives of prodrug design are to overcome barriers like poor solubility, stability, absorption and toxicity. An ideal prodrug is pharmacologically inert, transforms rapidly into the active form at the target site, and produces non-toxic metabolic fragments. Prodrugs are classified based on their structure and site of conversion. The applications of prodrugs include improving drug properties and delivery.
This document provides information on renal excretion of drugs. It discusses how the kidney is the primary route of elimination for water soluble, non-volatile and small molecule drugs. The basic functional unit of the kidney is the nephron, which filters drugs from the blood and reabsorbs or secretes them via processes like glomerular filtration, tubular secretion and reabsorption. Factors that influence renal excretion include the physicochemical properties of drugs as well as physiological and pathological factors. Renal impairment decreases drug clearance leading to prolonged drug exposure. Methods to assess renal function and adjust drug dosing based on renal function are also described.
factors affecting protein drug binding
significance of protein binding
drug related factors
protein related factors
drug interactions
patient related factors
Absorption of drugs from non per os extravascular administrationSuvarta Maru
Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Pharmacokinetics variations in Disease States.Faizan Akram
The biggest issue in PK/PD and drug therapy is variability in
response. Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs.
P glycoprotein is an efflux transporter that pumps certain drugs and toxins out of cells. It is expressed in the liver, kidneys, intestines and blood brain barrier, protecting tissues from harmful substances. P glycoprotein is a 170 kDa membrane protein composed of two symmetrical halves that contain transmembrane and ATP binding domains. It transports substrates by undergoing conformational changes upon ATP hydrolysis. P glycoprotein contributes to multi-drug resistance in cancer and limits oral absorption and brain penetration of many drugs. Genetic polymorphisms and drug interactions involving P glycoprotein inhibition or induction can significantly impact a drug's pharmacokinetics and toxicity.
This document discusses drug distribution, including tissue permeability, compartments for drug storage, plasma protein binding, kinetics of protein binding, factors affecting binding, and clinical significance. It notes that distribution is driven by concentration gradients and is not uniform across tissues. It also discusses redistribution between compartments over time. Protein binding influences absorption, distribution, metabolism, elimination and effects of drugs.
Protein binding kinetics studies how proteins interact with other molecules over time. An assistant professor from the Pharmaceutics department named Mrs. Mehetre Gitanjali S. presented on the topic of protein binding kinetics. The presentation covered the kinetics of how proteins bind to other molecules.
This document discusses protein drug binding, including the mechanisms, classes, and factors that influence it. It begins by introducing protein drug binding and defining it as the formation of a complex between a drug and a protein. This binding can be reversible or irreversible. There are several mechanisms of binding including hydrogen bonds, hydrophobic bonds, ionic bonds, and Van der Waals forces. Protein drug binding is important as it influences the absorption, distribution, metabolism, and excretion of drugs. The extent of protein binding is affected by characteristics of the drug and protein as well as disease states and interactions between drugs. In summary, this document provides an overview of the topic of protein drug binding, including the key concepts and significance.
The document discusses protein binding and factors affecting protein binding. It provides details on:
- The significance of protein binding is that bound drugs are inactive and have prolonged duration of action.
- Drugs can bind to blood components like plasma proteins, red blood cells, and tissues. The most significant binding is to human serum albumin.
- Factors that affect protein binding include the drug's physicochemical properties, its concentration, its affinity for proteins, the concentration and number of binding sites on proteins, drug interactions, and patient factors like age and disease states.
This document discusses drug distribution in the body. It begins by explaining that once a drug enters the bloodstream, it undergoes distribution and elimination processes that lower the plasma concentration over time. Distribution involves the reversible transfer of drugs between compartments like tissues, while elimination involves the irreversible loss of drugs from the body through metabolism and excretion. The rate and extent of distribution impacts the onset, intensity, and duration of a drug's effects. Distribution is non-uniform between tissues due to differences in perfusion rates and the extent to which different tissues take up drugs from plasma.
ABSORPTION OF DRUGS - NON PER ORAL - EXTRA VASCULAR ROUTESRam Kanth
Greetings!
Good Day to All..
This presentation is all about ABSORPTION OF DRUGS - NON PER ORAL - EXTRA VASCULAR ROUTES which covers about the various route of administration which are administered other than oral route like
1. Buccal / Sublingual
2. Rectal
3. Topical & Transdermal
4. Parenteral
5. Pulmonary & Intra nasal
6. Intra ocular &
7. Vaginal Administration
Your suggestion and comments are welcome for further improvement in my presentations.
Thank you all for your valuable time.
Disclaimer Note: Some contents in the presentation were taken from online sources which is purely used for education purpose and for any personal financial or commercial aspects. I thank all the source providers in online for your efforts and support in sharing of knowledge.
The document discusses drug absorption and factors that influence it. It defines drug absorption as the movement of an unchanged drug from the site of administration into systemic circulation. It describes the mechanisms of drug absorption including passive diffusion, carrier-mediated transport, and active transport. It discusses factors that can affect drug absorption like pharmaceutical factors (drug properties, dosage form), gastrointestinal factors (pH, transit time), and patient factors (age, disease states). The key points are that drug absorption involves dissolution then passage across the GI epithelium, and many intrinsic and extrinsic factors can impact the rate and extent of absorption.
The details about the elimination of the drug from the body by various methods. drug metabolism, drug transformation, drug elimination process. factors affecting.
A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh.
This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc
Protein binding describes the ability of drugs to form reversible or irreversible bonds with plasma and tissue proteins like albumin and alpha-1-acid glycoprotein. Only the unbound fraction of a drug interacts with receptors and is available to be metabolized or excreted, so protein binding significantly impacts a drug's effects, distribution, and clearance from the body. The degree of binding is determined by properties of both the drug and binding proteins, and can be altered through drug interactions that displace one drug from its binding sites.
The document provides an overview of drug metabolism. It discusses that drug metabolism is important as it converts lipophilic drugs to hydrophilic metabolites that can be readily excreted. The key sites of drug metabolism are the liver, GI tract, lungs and kidneys. Metabolism occurs via phase I and phase II reactions and can activate or deactivate drugs. Factors like enzymes, diet and disease can influence a drug's metabolism. Understanding metabolism is important for predicting drug interactions and toxicity.
This document provides an introduction to biopharmaceutics. It defines key terms like biopharmaceutics, pharmacokinetics, pharmacodynamics, absorption, distribution, metabolism, excretion, bioavailability, and bioavailable dose. It also outlines the four main processes involved in drug administration and therapy: the pharmaceutical processes of drug formulation, the pharmacokinetic processes of absorption, distribution, metabolism and excretion, the pharmacodynamic processes of a drug's mechanism of action, and the therapeutic processes of translating pharmacological effects to clinical effects. Finally, it notes that a dosage regimen specifies the time interval and dose size for taking a drug.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
Pharmacokinetics / Biopharmaceutics - IntroductionAreej Abu Hanieh
This document provides an introduction to pharmacokinetics, biopharmaceutics, pharmacodynamics, clinical pharmacokinetics, and toxicokinetics. It discusses how pharmacokinetics describes the absorption, distribution, metabolism and excretion of drugs in the body. Biopharmaceutics examines how the physical properties of drugs and dosage forms influence drug absorption. Pharmacodynamics studies the biochemical and physiological effects of drugs. Clinical pharmacokinetics applies these principles to optimize drug therapy for patients. Toxicokinetics and clinical toxicology evaluate adverse drug effects.
This document summarizes monoclonal antibodies and gene therapy. It discusses the discovery of monoclonal antibodies by Kohler and Milstein in 1975. It describes the production process of monoclonal antibodies which involves immunizing mice, fusing spleen cells with myeloma cells to form hybridomas, and cloning cell lines. The document also discusses types of monoclonal antibodies including murine, chimeric, and humanized, as well as applications in cancer therapy, diagnostics, and immunosuppression. Gene therapy techniques like ex vivo and in vivo delivery are summarized along with strategies for cancer like suicide gene therapy using thymidine kinase.
Absorption of drugs from non per os extravascular administrationSuvarta Maru
Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Pharmacokinetics variations in Disease States.Faizan Akram
The biggest issue in PK/PD and drug therapy is variability in
response. Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs.
P glycoprotein is an efflux transporter that pumps certain drugs and toxins out of cells. It is expressed in the liver, kidneys, intestines and blood brain barrier, protecting tissues from harmful substances. P glycoprotein is a 170 kDa membrane protein composed of two symmetrical halves that contain transmembrane and ATP binding domains. It transports substrates by undergoing conformational changes upon ATP hydrolysis. P glycoprotein contributes to multi-drug resistance in cancer and limits oral absorption and brain penetration of many drugs. Genetic polymorphisms and drug interactions involving P glycoprotein inhibition or induction can significantly impact a drug's pharmacokinetics and toxicity.
This document discusses drug distribution, including tissue permeability, compartments for drug storage, plasma protein binding, kinetics of protein binding, factors affecting binding, and clinical significance. It notes that distribution is driven by concentration gradients and is not uniform across tissues. It also discusses redistribution between compartments over time. Protein binding influences absorption, distribution, metabolism, elimination and effects of drugs.
Protein binding kinetics studies how proteins interact with other molecules over time. An assistant professor from the Pharmaceutics department named Mrs. Mehetre Gitanjali S. presented on the topic of protein binding kinetics. The presentation covered the kinetics of how proteins bind to other molecules.
This document discusses protein drug binding, including the mechanisms, classes, and factors that influence it. It begins by introducing protein drug binding and defining it as the formation of a complex between a drug and a protein. This binding can be reversible or irreversible. There are several mechanisms of binding including hydrogen bonds, hydrophobic bonds, ionic bonds, and Van der Waals forces. Protein drug binding is important as it influences the absorption, distribution, metabolism, and excretion of drugs. The extent of protein binding is affected by characteristics of the drug and protein as well as disease states and interactions between drugs. In summary, this document provides an overview of the topic of protein drug binding, including the key concepts and significance.
The document discusses protein binding and factors affecting protein binding. It provides details on:
- The significance of protein binding is that bound drugs are inactive and have prolonged duration of action.
- Drugs can bind to blood components like plasma proteins, red blood cells, and tissues. The most significant binding is to human serum albumin.
- Factors that affect protein binding include the drug's physicochemical properties, its concentration, its affinity for proteins, the concentration and number of binding sites on proteins, drug interactions, and patient factors like age and disease states.
This document discusses drug distribution in the body. It begins by explaining that once a drug enters the bloodstream, it undergoes distribution and elimination processes that lower the plasma concentration over time. Distribution involves the reversible transfer of drugs between compartments like tissues, while elimination involves the irreversible loss of drugs from the body through metabolism and excretion. The rate and extent of distribution impacts the onset, intensity, and duration of a drug's effects. Distribution is non-uniform between tissues due to differences in perfusion rates and the extent to which different tissues take up drugs from plasma.
ABSORPTION OF DRUGS - NON PER ORAL - EXTRA VASCULAR ROUTESRam Kanth
Greetings!
Good Day to All..
This presentation is all about ABSORPTION OF DRUGS - NON PER ORAL - EXTRA VASCULAR ROUTES which covers about the various route of administration which are administered other than oral route like
1. Buccal / Sublingual
2. Rectal
3. Topical & Transdermal
4. Parenteral
5. Pulmonary & Intra nasal
6. Intra ocular &
7. Vaginal Administration
Your suggestion and comments are welcome for further improvement in my presentations.
Thank you all for your valuable time.
Disclaimer Note: Some contents in the presentation were taken from online sources which is purely used for education purpose and for any personal financial or commercial aspects. I thank all the source providers in online for your efforts and support in sharing of knowledge.
The document discusses drug absorption and factors that influence it. It defines drug absorption as the movement of an unchanged drug from the site of administration into systemic circulation. It describes the mechanisms of drug absorption including passive diffusion, carrier-mediated transport, and active transport. It discusses factors that can affect drug absorption like pharmaceutical factors (drug properties, dosage form), gastrointestinal factors (pH, transit time), and patient factors (age, disease states). The key points are that drug absorption involves dissolution then passage across the GI epithelium, and many intrinsic and extrinsic factors can impact the rate and extent of absorption.
The details about the elimination of the drug from the body by various methods. drug metabolism, drug transformation, drug elimination process. factors affecting.
A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh.
This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc
Protein binding describes the ability of drugs to form reversible or irreversible bonds with plasma and tissue proteins like albumin and alpha-1-acid glycoprotein. Only the unbound fraction of a drug interacts with receptors and is available to be metabolized or excreted, so protein binding significantly impacts a drug's effects, distribution, and clearance from the body. The degree of binding is determined by properties of both the drug and binding proteins, and can be altered through drug interactions that displace one drug from its binding sites.
The document provides an overview of drug metabolism. It discusses that drug metabolism is important as it converts lipophilic drugs to hydrophilic metabolites that can be readily excreted. The key sites of drug metabolism are the liver, GI tract, lungs and kidneys. Metabolism occurs via phase I and phase II reactions and can activate or deactivate drugs. Factors like enzymes, diet and disease can influence a drug's metabolism. Understanding metabolism is important for predicting drug interactions and toxicity.
This document provides an introduction to biopharmaceutics. It defines key terms like biopharmaceutics, pharmacokinetics, pharmacodynamics, absorption, distribution, metabolism, excretion, bioavailability, and bioavailable dose. It also outlines the four main processes involved in drug administration and therapy: the pharmaceutical processes of drug formulation, the pharmacokinetic processes of absorption, distribution, metabolism and excretion, the pharmacodynamic processes of a drug's mechanism of action, and the therapeutic processes of translating pharmacological effects to clinical effects. Finally, it notes that a dosage regimen specifies the time interval and dose size for taking a drug.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
Pharmacokinetics / Biopharmaceutics - IntroductionAreej Abu Hanieh
This document provides an introduction to pharmacokinetics, biopharmaceutics, pharmacodynamics, clinical pharmacokinetics, and toxicokinetics. It discusses how pharmacokinetics describes the absorption, distribution, metabolism and excretion of drugs in the body. Biopharmaceutics examines how the physical properties of drugs and dosage forms influence drug absorption. Pharmacodynamics studies the biochemical and physiological effects of drugs. Clinical pharmacokinetics applies these principles to optimize drug therapy for patients. Toxicokinetics and clinical toxicology evaluate adverse drug effects.
This document summarizes monoclonal antibodies and gene therapy. It discusses the discovery of monoclonal antibodies by Kohler and Milstein in 1975. It describes the production process of monoclonal antibodies which involves immunizing mice, fusing spleen cells with myeloma cells to form hybridomas, and cloning cell lines. The document also discusses types of monoclonal antibodies including murine, chimeric, and humanized, as well as applications in cancer therapy, diagnostics, and immunosuppression. Gene therapy techniques like ex vivo and in vivo delivery are summarized along with strategies for cancer like suicide gene therapy using thymidine kinase.
The document summarizes the history and development of drug regulation laws in the United States from the early 1900s to present day. Key acts and amendments established safety testing requirements for drugs, created the FDA, and defined the modern drug approval process including preclinical research and multi-phase clinical trials. The modern system aims to balance drug accessibility while ensuring safety and efficacy through a rigorous review and oversight process from development through post-marketing.
This document discusses antibody-directed enzyme-prodrug therapy (ADEPT) for cancer treatment. ADEPT involves administering an antibody-enzyme fusion protein that localizes an enzyme to the tumor, followed by a prodrug that is non-toxic until converted to a cytotoxic drug by the localized enzyme. The document outlines the mechanism of ADEPT, various enzymes and prodrugs used, advances like improved antibody-enzyme complexes and clearance, phase I clinical trials results, and mathematical models to optimize ADEPT dosing and pharmacokinetics. It concludes that while clinical trials proved ADEPT's potential, further research is still needed to address toxicities in order to develop ADEPT as a successful
DESIGN, PREPARATION, EVALUATION, COMPATIBILITY AND INVITRO STUDIES OF NAPROXE...Maksud Al- Hasan (Mahim)
ABSTRACT
The rationale of the present study was to design and prepare a combination product of naproxen and esomeprazole tablet by layer by layer tableting method. In this method shellac, cellulose acetate phthalate, methacrylic acid (copolymers), polyvinyl acetate phthalate and hypromellose phthalate were used as an enteric coating agent, to provide delayed action of naproxen, and esomeprazole was combined as an immediate release part which was added as a drug layer around the enteric coated naproxen core through a coating suspension.
Oral glucosamine supplementation has low bioavailability in horses, with only about 2.5% being absorbed. However, several studies have found improvements in gait parameters in lame horses supplemented with glucosamine. While the mechanism is unclear given low absorption, glucosamine may have an anti-inflammatory effect. Future research is needed to improve absorption and determine if long-term supplementation can slow joint deterioration.
This document summarizes a seminar on drug excipient compatibility studies, which are an important part of preformulation studies. It defines incompatibility and the different types. The objectives and aspects of compatibility tests are discussed. The key steps in a compatibility study including sample preparation, storage conditions, and analytical techniques are outlined. Specific techniques like DSC and TLC are described along with examples. Common known incompatibilities between functional groups and specific excipients are listed. The importance of excipient impurities and compatibility studies for different dosage forms like aerosols and parenterals is highlighted.
Novel Tocopherol Naproxen Ester Pro Drug Madan Baral
The document describes the design, synthesis, and evaluation of novel naproxen ester prodrugs containing alpha-tocopherol or beta-tocopherol. The prodrugs were synthesized using a general procedure and characterized using various analytical techniques. Pharmacokinetic studies in rabbits found the prodrugs had higher bioavailability than naproxen alone. Pharmacodynamic tests in rats showed the prodrugs had strong anti-inflammatory effects in paw and air pouch models, with a significant reduction in gastric lesions compared to naproxen. Overall, the naproxen-tocopherol ester prodrugs showed promising anti-inflammatory properties with protective effects against gastric injury.
This document outlines the history of drug development and approval processes in the United States from 1820 to 1997. It describes key milestones and legislation that established regulations for new drug applications (NDAs). NDAs were first required in 1938 to show drug safety, and in 1962 were amended to require proof of efficacy. The FDA now reviews NDAs to ensure the benefits of new drugs outweigh the risks based on clinical trial data.
This document discusses hard and soft drugs. Hard drugs are biologically active and non-metabolizable, while soft drugs are designed to have predictable and controllable metabolism into nontoxic products after their therapeutic effect. Soft drugs have advantages like avoiding toxic metabolites and increasing the therapeutic index. They are divided into categories like soft analogs, activated soft compounds, natural soft drugs, and those based on active or inactive metabolite approaches. The document provides examples to illustrate differences between hard drugs, soft drugs, and prodrugs.
This document discusses various types of drugs, their usage and effects. It covers stimulants like amphetamines, cocaine and methamphetamine. It also discusses depressants like alcohol, sleeping pills and narcotics like morphine, codeine and heroin. Marijuana usage statistics for teens are provided. The document warns that all drugs can be addictive and harmful.
This document provides an overview of the new drug development and approval process. It discusses pre-clinical studies including chemistry, pharmacology, toxicology and clinical trials in three phases to test safety and efficacy in humans. It also describes the FDA approval process including submission of a New Drug Application and pre-approval plant inspection. Key aspects like formulation development, selection of excipients and container closure system, and drug product labeling are summarized.
Genes carry hereditary information and encode proteins. Gene therapy aims to treat diseases by correcting defective genes through various approaches like inserting a normal gene or repairing an abnormal gene. Early research in the 1980s involved inserting human genes into bacteria. The first human gene therapy treated a girl for SCID in 1990 by inserting a normal gene into her white blood cells. Viral vectors like retroviruses and adenoviruses as well as non-viral methods can deliver genes, but all methods face challenges like short-lived effects, immune responses, and difficulties treating multi-gene disorders and diseases. While progress has been made, setbacks include a death in 1999 from an immune response and some children developing cancer from viral vectors.
Phase 1 clinical trials are the first studies conducted in humans of a new drug or treatment. They aim to determine the drug's safety and tolerability, identify the maximum tolerated dose, and understand the drug's pharmacokinetics. Phase 1 trials typically involve small groups of healthy volunteers or patients and start with low doses that are gradually increased. The results of phase 1 trials provide information needed to design subsequent phase 2 and 3 trials to further evaluate efficacy.
2016-11-28 Mentlife seminar: Pharmaceutical Drug Development; An Overall Pers...MentLife
This seminar provided an understanding of modern pharmaceutical drug development – the different phases of drug development and insight into different jobs.
The document provides an overview of the drug development process. It discusses the major stages of clinical trials from Phase I to Phase IV that drugs must go through for testing and approval. The goals are to determine safety, efficacy, appropriate dosing, and identify any adverse effects. Rigorous clinical trials with control groups, randomization, and large sample sizes are necessary to provide substantial evidence for approval. The overall process takes an average of about 100 months from initial synthesis to approval.
Naila Kanwal's document summarizes the new drug development and approval process. It describes the preclinical research phase involving animal and lab testing to determine safety and effectiveness. It then explains the clinical trial phases involving human subjects to further evaluate these factors. The document outlines the steps of submitting an Investigational New Drug application to the FDA for review and potential approval or requests for additional information before studies can begin. The overall process is designed to demonstrate a new drug is safe and effective for its intended use before being approved and marketed to the public.
The document discusses computer aided drug design (CADD). It describes CADD as using computational methods to aid in drug discovery and design. Some key points include:
- CADD uses tools like bioinformatics, cheminformatics, and computational chemistry to discover, study, and enhance drug molecules.
- Target-based and ligand-based approaches are two main computational methods used in CADD. Target-based approaches use structural information about biological targets while ligand-based approaches analyze characteristics of known active ligands.
- Other stages of drug design discussed include lead identification, lead optimization, docking simulations to model drug-target binding, and pre-clinical trials to evaluate drug properties before human testing.
Introduction of pharmacology first yearsssuser4c546a
Pharmacology is the study of how drugs interact with living organisms. It includes pharmacodynamics, which examines what the drug does to the body, and pharmacokinetics, which examines what the body does to the drug. Drugs undergo a development process including preclinical testing in animals and clinical trials in humans before approval. Many factors can influence a drug's effects, including dosage, route of administration, metabolism, and interactions with other drugs or the body. Adverse reactions are also an important consideration in pharmacology.
GENERAL PHARMACOLOGY PPT. DT 2nd year.pptxSafuraIjaz2
This document provides an overview of general pharmacology concepts. It defines key terms like pharmacology, pharmacokinetics, and pharmacodynamics. It discusses drug sources, routes of administration, absorption, distribution, biotransformation, elimination, and dose-response relationships. The document also explains membrane transporters, factors affecting drug absorption and metabolism, drug clearance, and the kidney's role in drug excretion.
Therapeutic drug monitoring (TDM) involves analyzing drug concentrations in blood to ensure dosage is therapeutic and not toxic. TDM is indicated when the therapeutic index is narrow, drug effects vary between patients, or changes in a patient's condition could affect drug levels. Common drugs monitored include cardiac medications, antibiotics, antiepileptics, psychotherapeutics, and immunosuppressants. Factors like absorption, distribution, metabolism, and excretion influence circulating drug concentrations.
The document discusses key principles of pharmacology including:
1. Pharmacology is the study of drugs and their interaction with living systems, specifically how they bind to regulatory molecules and affect body processes.
2. Pharmacokinetics describes what the body does to drugs including absorption, distribution, metabolism, and excretion.
3. Pharmacodynamics describes what drugs do to the body including their effects, mechanisms of action, and interactions with receptors.
Therapeutic drug monitoring involves measuring drug levels in patients' blood to ensure drug dosages produce therapeutic effects without toxicity. Several health professionals coordinate timing of blood collection, measuring drug levels, and reporting results to physicians for adjusting dosages. Therapeutic drug monitoring is especially important for drugs with a narrow range between therapeutic and toxic levels due to variability in absorption, distribution, metabolism and excretion between individuals. Proper collection and handling of blood samples is critical for obtaining accurate drug level measurements.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the study of how drugs interact with living systems, including their effects, absorption, distribution, metabolism and excretion. The document outlines the key branches and concepts of pharmacology, including pharmacokinetics, pharmacodynamics, drug sources, nomenclature, administration routes, and factors affecting drug absorption.
Basic Princioles of Pharmacokinetics 05 02 2023 BAA.pptxmaamedokuah233
The document discusses the basic principles of pharmacokinetics, which is the study of what the body does to drugs. It covers the key processes of absorption, distribution, metabolism, and excretion (ADME) that drugs undergo in the body. Absorption refers to how drugs enter the bloodstream, distribution is the movement of drugs between tissues, metabolism chemically alters drugs to aid excretion, and excretion is how drugs are removed from the body. Understanding a drug's pharmacokinetics is important for ensuring safe and effective use.
Metabolism plays an important role in drug discovery by providing information on metabolic stability, metabolic profiles, drug-drug interactions, and pharmacokinetics. Advances in fields like pharmacogenetics, pharmacogenomics, and drug transporters have expanded understanding of metabolic pathways and genetic influences. In vitro studies using liver microsomes and recombinant enzymes help identify metabolic enzymes and potential for drug interactions. Drug metabolism occurs in two phases: phase I introduces functional groups through reactions like oxidation, while phase II involves conjugating the drug with endogenous compounds like glucuronic acid to make it more soluble for excretion. Understanding metabolism aids in predicting toxicity, efficacy of drug candidates, and optimizing properties like stability.
The document discusses fundamentals of pharmacology including pharmacokinetics and pharmacodynamics. Pharmacokinetics describes how the body affects a drug through absorption, distribution, metabolism and excretion. Key concepts covered include bioavailability, volume of distribution, drug metabolism by cytochrome P450 enzymes, and zero-order and first-order kinetics. Clinical drug trials are also summarized, outlining the purpose and design of phases 0 through 4.
Medicinal chemistry is the interdisciplinary field that combines chemistry and biology in the research and development of new pharmaceutical drugs. The goals of medicinal chemistry include discovering and designing biologically active compounds, determining their mode of action at the molecular level, and developing structure-activity relationship data to guide future drug design. Key aspects of medicinal chemistry include computer-aided drug design, drug synthesis and optimization, determining drug properties such as bioavailability and stability, and understanding the drug approval process. The ultimate goal is to develop safe and effective therapeutic agents to treat diseases.
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug’s effect on the body more closely. The four main parameters generally examined by this field include absorption, distribution, metabolism, and excretion (ADME). Wielding an understanding of these processes allows practitioners the flexibility to prescribe and administer medications that will provide the greatest benefit at the lowest risk and allow them to make adjustments as necessary, given the varied physiology and lifestyles of patients.
When a provider prescribes medication, it is with the ultimate goal of a therapeutic outcome while minimizing adverse reactions. A thorough understanding of pharmacokinetics is essential in building treatment plans involving medications. Pharmacokinetics, as a field, attempts to summarize the movement of drugs throughout the body and the actions of the body on the drug. By using the above terms, theories, and equations, practitioners can better estimate the locations and concentrations of a drug in different areas of the body.
The appropriate concentration needed to obtain the desired effect and the amount needed for a higher chance of adverse reactions is determined through laboratory testing. Using the equations given above, a clinician can easily estimate safe medication dosing over a period of time and how long it will take for a medication to leave a patient’s system. These are, however, statistically-based estimations, influenced by differences in the drug dosage form and patient pathophysiology. This is why a deep understanding of these concepts is essential in medical practice so that improvisation is possible when the clinical situation requires it.
This document provides definitions and information related to general pharmacology for physiotherapists. It defines key terms like pharmacology, pharmacodynamics, pharmacokinetics, and discusses topics like drug sources, routes of administration, absorption, distribution, metabolism, excretion, and mechanisms of drug action including drug receptors. The summary covers essential concepts in a concise manner.
GENERAL PHARMACOLOGY PPT. DT 2nd year.pptxSafuraIjaz2
1. The document discusses general pharmacology, defining key terms like pharmacokinetics, pharmacodynamics, and sources of drugs from plants, animals, microorganisms, and synthesis.
2. It covers routes of drug administration including enteral, parenteral, inhalation, and topical routes. Drug absorption and factors affecting it are explained.
3. The processes of drug distribution, membrane transporters, biotransformation, and elimination are summarized along with dose-response relationships and factors influencing pharmacology.
This document provides an overview of pharmacology, including:
1) Pharmacology is the study of drugs and their interaction with living systems, specifically how they bind to regulatory molecules and affect body processes.
2) It is divided into medical pharmacology which deals with drug use for diagnosis and treatment of diseases, and clinical pharmacology which studies drug effects in patients and healthy individuals.
3) Key divisions of pharmacology are pharmacokinetics (what body does to drug), pharmacodynamics (what drug does to body), and pharmacogenomics (effects of genetic differences on drug responses).
Introduction to pharmacology Part 2 ppt.pptxImranUllah81
This document discusses pharmacokinetics and pharmacodynamics. It defines pharmacokinetics as the study of how the body affects drugs and pharmacodynamics as how drugs affect the body. Key concepts covered include absorption, distribution, metabolism, excretion, bioavailability, half-life, therapeutic index, mechanisms of drug action including receptors, and factors that influence drug effects such as synergism, antagonism, and drug interactions.
This document provides an overview of general principles of pharmacology. It discusses key topics including:
- The definition and study of pharmacology and the types of drug names used.
- The four basic pharmacokinetic processes of drug absorption, distribution, metabolism and excretion that determine a drug's concentration at its site of action.
- Factors that influence drug passage across membranes and the different mechanisms of passive and active transport.
- The relationship between dose, plasma drug concentration, and drug response over time.
- How drugs produce their effects through interaction with receptors and the concepts of affinity, efficacy and agonist/antagonist activity.
- Factors influencing drug-drug interactions and the management of adverse drug
This document provides an overview of drug metabolism. It discusses that drugs must undergo metabolism to become water soluble enough to be excreted from the body. Metabolism occurs in two phases - phase I involves reactions like oxidation and phase II involves conjugation. Key enzymes like cytochrome P450 catalyze phase I reactions in the liver. Factors like age, sex, disease state, environment, and genetic variation can impact a person's drug metabolism and influence how drugs are processed in their body. Understanding metabolism is important for predicting drug interactions and individualizing drug therapy.
This document provides an overview of key concepts in pharmacology. It defines pharmacology and its branches, which include pharmacokinetics and pharmacodynamics. It discusses sources of drugs, routes of drug administration like oral, parenteral, and topical, and factors that determine administration route. It also covers ligands and their types like agonists and antagonists. In summary, the document outlines the fundamental principles of pharmacology including how drugs are developed, distributed in the body, and exert their effects.
introduction to General pharmacology by : Dr Debasish PradhanDr Debasish Pradhan
Introduction to general Pharmacology, Routes of drug administration with their advantages and Disadvantages, Factors affecting routes of drug administration.
Similar to Drug development prodrug PhD seminar mehdi akhlaghi (20)
Discovery of An Apparent Red, High-Velocity Type Ia Supernova at 𝐳 = 2.9 wi...Sérgio Sacani
We present the JWST discovery of SN 2023adsy, a transient object located in a host galaxy JADES-GS
+
53.13485
−
27.82088
with a host spectroscopic redshift of
2.903
±
0.007
. The transient was identified in deep James Webb Space Telescope (JWST)/NIRCam imaging from the JWST Advanced Deep Extragalactic Survey (JADES) program. Photometric and spectroscopic followup with NIRCam and NIRSpec, respectively, confirm the redshift and yield UV-NIR light-curve, NIR color, and spectroscopic information all consistent with a Type Ia classification. Despite its classification as a likely SN Ia, SN 2023adsy is both fairly red (
�
(
�
−
�
)
∼
0.9
) despite a host galaxy with low-extinction and has a high Ca II velocity (
19
,
000
±
2
,
000
km/s) compared to the general population of SNe Ia. While these characteristics are consistent with some Ca-rich SNe Ia, particularly SN 2016hnk, SN 2023adsy is intrinsically brighter than the low-
�
Ca-rich population. Although such an object is too red for any low-
�
cosmological sample, we apply a fiducial standardization approach to SN 2023adsy and find that the SN 2023adsy luminosity distance measurement is in excellent agreement (
≲
1
�
) with
Λ
CDM. Therefore unlike low-
�
Ca-rich SNe Ia, SN 2023adsy is standardizable and gives no indication that SN Ia standardized luminosities change significantly with redshift. A larger sample of distant SNe Ia is required to determine if SN Ia population characteristics at high-
�
truly diverge from their low-
�
counterparts, and to confirm that standardized luminosities nevertheless remain constant with redshift.
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
Discovery of Merging Twin Quasars at z=6.05Sérgio Sacani
We report the discovery of two quasars at a redshift of z = 6.05 in the process of merging. They were
serendipitously discovered from the deep multiband imaging data collected by the Hyper Suprime-Cam (HSC)
Subaru Strategic Program survey. The quasars, HSC J121503.42−014858.7 (C1) and HSC J121503.55−014859.3
(C2), both have luminous (>1043 erg s−1
) Lyα emission with a clear broad component (full width at half
maximum >1000 km s−1
). The rest-frame ultraviolet (UV) absolute magnitudes are M1450 = − 23.106 ± 0.017
(C1) and −22.662 ± 0.024 (C2). Our crude estimates of the black hole masses provide log 8.1 0. ( ) M M BH = 3
in both sources. The two quasars are separated by 12 kpc in projected proper distance, bridged by a structure in the
rest-UV light suggesting that they are undergoing a merger. This pair is one of the most distant merging quasars
reported to date, providing crucial insight into galaxy and black hole build-up in the hierarchical structure
formation scenario. A companion paper will present the gas and dust properties captured by Atacama Large
Millimeter/submillimeter Array observations, which provide additional evidence for and detailed measurements of
the merger, and also demonstrate that the two sources are not gravitationally lensed images of a single quasar.
Unified Astronomy Thesaurus concepts: Double quasars (406); Quasars (1319); Reionization (1383); High-redshift
galaxies (734); Active galactic nuclei (16); Galaxy mergers (608); Supermassive black holes (1663)
JAMES WEBB STUDY THE MASSIVE BLACK HOLE SEEDSSérgio Sacani
The pathway(s) to seeding the massive black holes (MBHs) that exist at the heart of galaxies in the present and distant Universe remains an unsolved problem. Here we categorise, describe and quantitatively discuss the formation pathways of both light and heavy seeds. We emphasise that the most recent computational models suggest that rather than a bimodal-like mass spectrum between light and heavy seeds with light at one end and heavy at the other that instead a continuum exists. Light seeds being more ubiquitous and the heavier seeds becoming less and less abundant due the rarer environmental conditions required for their formation. We therefore examine the different mechanisms that give rise to different seed mass spectrums. We show how and why the mechanisms that produce the heaviest seeds are also among the rarest events in the Universe and are hence extremely unlikely to be the seeds for the vast majority of the MBH population. We quantify, within the limits of the current large uncertainties in the seeding processes, the expected number densities of the seed mass spectrum. We argue that light seeds must be at least 103 to 105 times more numerous than heavy seeds to explain the MBH population as a whole. Based on our current understanding of the seed population this makes heavy seeds (Mseed > 103 M⊙) a significantly more likely pathway given that heavy seeds have an abundance pattern than is close to and likely in excess of 10−4 compared to light seeds. Finally, we examine the current state-of-the-art in numerical calculations and recent observations and plot a path forward for near-future advances in both domains.
Evaluation and Identification of J'BaFofi the Giant Spider of Congo and Moke...MrSproy
ABSTRACT
The J'BaFofi, or "Giant Spider," is a mainly legendary arachnid by reportedly inhabiting the dense rain forests of
the Congo. As despite numerous anecdotal accounts and cultural references, the scientific validation remains more elusive.
My study aims to proper evaluate the existence of the J'BaFofi through the analysis of historical reports,indigenous
testimonies and modern exploration efforts.
Signatures of wave erosion in Titan’s coastsSérgio Sacani
The shorelines of Titan’s hydrocarbon seas trace flooded erosional landforms such as river valleys; however, it isunclear whether coastal erosion has subsequently altered these shorelines. Spacecraft observations and theo-retical models suggest that wind may cause waves to form on Titan’s seas, potentially driving coastal erosion,but the observational evidence of waves is indirect, and the processes affecting shoreline evolution on Titanremain unknown. No widely accepted framework exists for using shoreline morphology to quantitatively dis-cern coastal erosion mechanisms, even on Earth, where the dominant mechanisms are known. We combinelandscape evolution models with measurements of shoreline shape on Earth to characterize how differentcoastal erosion mechanisms affect shoreline morphology. Applying this framework to Titan, we find that theshorelines of Titan’s seas are most consistent with flooded landscapes that subsequently have been eroded bywaves, rather than a uniform erosional process or no coastal erosion, particularly if wave growth saturates atfetch lengths of tens of kilometers.
Compositions of iron-meteorite parent bodies constrainthe structure of the pr...Sérgio Sacani
Magmatic iron-meteorite parent bodies are the earliest planetesimals in the Solar System,and they preserve information about conditions and planet-forming processes in thesolar nebula. In this study, we include comprehensive elemental compositions andfractional-crystallization modeling for iron meteorites from the cores of five differenti-ated asteroids from the inner Solar System. Together with previous results of metalliccores from the outer Solar System, we conclude that asteroidal cores from the outerSolar System have smaller sizes, elevated siderophile-element abundances, and simplercrystallization processes than those from the inner Solar System. These differences arerelated to the formation locations of the parent asteroids because the solar protoplane-tary disk varied in redox conditions, elemental distributions, and dynamics at differentheliocentric distances. Using highly siderophile-element data from iron meteorites, wereconstruct the distribution of calcium-aluminum-rich inclusions (CAIs) across theprotoplanetary disk within the first million years of Solar-System history. CAIs, the firstsolids to condense in the Solar System, formed close to the Sun. They were, however,concentrated within the outer disk and depleted within the inner disk. Future modelsof the structure and evolution of the protoplanetary disk should account for this dis-tribution pattern of CAIs.
Physics Investigatory Project on transformers. Class 12thpihuart12
Physics investigatory project on transformers with required details for 12thes. with index, theory, types of transformers (with relevant images), procedure, sources of error, aim n apparatus along with bibliography🗃️📜. Please try to add your own imagination rather than just copy paste... Hope you all guys friends n juniors' like it. peace out✌🏻✌🏻
This presentation offers a general idea of the structure of seed, seed production, management of seeds and its allied technologies. It also offers the concept of gene erosion and the practices used to control it. Nursery and gardening have been widely explored along with their importance in the related domain.
Presentation of our paper, "Towards Quantitative Evaluation of Explainable AI Methods for Deepfake Detection", by K. Tsigos, E. Apostolidis, S. Baxevanakis, S. Papadopoulos, V. Mezaris. Presented at the ACM Int. Workshop on Multimedia AI against Disinformation (MAD’24) of the ACM Int. Conf. on Multimedia Retrieval (ICMR’24), Thailand, June 2024. https://doi.org/10.1145/3643491.3660292 https://arxiv.org/abs/2404.18649
Software available at https://github.com/IDT-ITI/XAI-Deepfakes
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
Drug development prodrug PhD seminar mehdi akhlaghi
1. 1
Sharif University of Technology
Department of Chemistry
Ph.D. Seminar I
By: Mehdi Akhlaghi
Supervisor: Prof. Ali Pourjavadi
Kimia hall
Tuesday, June 21, 2011 (3:00 p.m.)
31 khordad 1390
Drug Discovery and Development:
Prodrug Strategy to Increase
Success
2. 2
How are drugs discovered and developed?How are drugs discovered and developed?
Prodrug strategy will increase success of process ?Prodrug strategy will increase success of process ?
Drug Discovery and
Development
By: Mehdi Akhlaghi Supervisor: Dr. Pourjavadi
3. 3
FDA Definition of a Drug
Any chemical agent which effects any biological processAny chemical agent which effects any biological process
““ An active ingredient that is intended to furnish pharmacological activity orAn active ingredient that is intended to furnish pharmacological activity or
other direct effect in the diagnosis, cure, mitigation, treatment, orother direct effect in the diagnosis, cure, mitigation, treatment, or
prevention of a disease, or to affect the structure of any function of theprevention of a disease, or to affect the structure of any function of the
human body, but does not include intermediates used in the synthesis ofhuman body, but does not include intermediates used in the synthesis of
such ingredient.”such ingredient.”
4. 4
5,000–10,000
Screened
250
Enter Preclinical
Testing
5
Enter
Clinical
Testing
1
Approved by
the FDA
16
14
12
10
8
6
4
2
0
Net Cost: $802 million
invested over 15 yearsSource: DiMasi et al. 2003, Tufts
Years
Discovery:
(2-10 years)
Phase I: 20-80 healthy
volunteers to determine
safety & dosage
Phase III: 1000-5000
volunteers to monitor
adverse reactions to
long-term use
Phase II: 100-
300 volunteers
to look for
efficacy & side
effects
FDA Review
ApprovalAdditional
post-market
testing
Preclinical:
laboratory &
animal tests
Compound Success
Rates by Stage
R&D Is Risky & Costly
5. 5
Choosing a Disease
• Most research is carriedMost research is carried
out on diseases whichout on diseases which
afflict “first world”afflict “first world”
countries: (e.g. cancer,countries: (e.g. cancer,
cardiovascular diseases,cardiovascular diseases,
depression, diabetes, flu,depression, diabetes, flu,
migraine, obesity).migraine, obesity).
6. 6
Identifying a Drug Target
• Drug Target = specific macromolecule, orDrug Target = specific macromolecule, or
biological system, which the drug willbiological system, which the drug will
interact with.interact with.
7. 7
Proposing new drug (Drug Discovery)
Drug source and selection approachesDrug source and selection approaches
• Irrational approachIrrational approach
• Rational approachRational approach
• Antisense ApproachAntisense Approach
• RNAi ApproachRNAi Approach
• BiologicsBiologics
• Gene TherapyGene Therapy
• ..
• ..
• .. O
HO
H
N
HO
CH3
O
O
H
N
O
CH3
O CH3
O
CH3
O
CH3O
H
N
HO
CH3
codeine
heroin
morphine
9. 9
Choosing the Bioassay
• Definitions:Definitions:
• In vitroIn vitro:: In an artificial environment, as in aIn an artificial environment, as in a
test tube or culture mediatest tube or culture media
• In vivoIn vivo:: In the living body, referring to testsIn the living body, referring to tests
conducted in living animalsconducted in living animals
• Ex vivoEx vivo:: Usually refers to doing the test on aUsually refers to doing the test on a
tissue taken from a living organism.tissue taken from a living organism.
10. 10
What is Pharmacology ?
PharmacologyPharmacology
Pharmacokinetics Pharmacodynamics
What the body does to drug What the drug does to body
ToxicologyToxicology,, carcinogenicity, mutagenicitycarcinogenicity, mutagenicity
Animal Tests, In Vitro Assays, and In Silico MethodsAnimal Tests, In Vitro Assays, and In Silico Methods
Formulations and Delivery SystemsFormulations and Delivery Systems
14. 14
Drug Metabolism
• Most metabolic products areMost metabolic products are less pharmacologically activeless pharmacologically active
• Close relationshipClose relationship between thebetween the biotransformation of drugsbiotransformation of drugs
andand normal biochemical processesnormal biochemical processes occurring in the body:occurring in the body:
• Metabolism of drugs involves many pathways associated with theMetabolism of drugs involves many pathways associated with the
synthesis of endogenous substrates such as steroid hormones, cholesterolsynthesis of endogenous substrates such as steroid hormones, cholesterol
and bile acidsand bile acids
• Many of the enzymes involved in drug metabolism are principallyMany of the enzymes involved in drug metabolism are principally
designed for the metabolism of endogenous compoundsdesigned for the metabolism of endogenous compounds
• These enzymes metabolize drugs only because theThese enzymes metabolize drugs only because the drugs resemble thedrugs resemble the
natural compoundnatural compound
15. 15
Phases of Drug Metabolism• Phase I ReactionsPhase I Reactions
• Convert parent compound into a more polar (=hydrophilic) metabolite byConvert parent compound into a more polar (=hydrophilic) metabolite by
adding or unmasking functional groupsadding or unmasking functional groups (-OH, -SH, -NH(-OH, -SH, -NH22, -COOH, etc.), -COOH, etc.)
• Often these metabolites are inactiveOften these metabolites are inactive
• May be sufficiently polar to be excreted readilyMay be sufficiently polar to be excreted readily
• Phase II ReactionsPhase II Reactions
• Conjugation with endogenous substrateConjugation with endogenous substrate to further increase aqueousto further increase aqueous
solubilitysolubility
• Conjugation with glucuronideConjugation with glucuronide, sulfate, acetate, amino acid, sulfate, acetate, amino acid
Liver is principal site of drug metabolism:Liver is principal site of drug metabolism:
• Other sites include the gut, lungs, skin and kidneysOther sites include the gut, lungs, skin and kidneys
• For orally administered compounds, there is theFor orally administered compounds, there is the
““First Pass Effect”First Pass Effect”
• Intestinal metabolismIntestinal metabolism
• Liver metabolismLiver metabolism
• Enterohepatic recyclingEnterohepatic recycling
• Gut microorganisms - glucuronidasesGut microorganisms - glucuronidases
16. 16
Drug Metabolism - Phase I
• Phase I ReactionsPhase I Reactions
• OxidationOxidation
• ReductionReduction
• Hydrolytic cleavageHydrolytic cleavage
• Alkylation (Methylation)Alkylation (Methylation)
• DealkylationDealkylation
• Ring cyclizationRing cyclization
• N-carboxylationN-carboxylation
• DimerizationDimerization
• TransamidationTransamidation
• IsomerizationIsomerization
• DecarboxylationDecarboxylation
17. 17
Drug Metabolism - Phase II
• Conjugation reactionsConjugation reactions
• GlucuronidationGlucuronidation by UDP-Glucuronosyltransferase:by UDP-Glucuronosyltransferase:
(on -OH, -COOH, -NH(on -OH, -COOH, -NH22, -SH groups), -SH groups)
• SulfationSulfation by Sulfotransferase:by Sulfotransferase:
(on -NH2, -SO(on -NH2, -SO22NHNH22, -OH groups), -OH groups)
• AcetylationAcetylation by acetyltransferase:by acetyltransferase:
(on -NH(on -NH22, -SO, -SO22NHNH22, -OH groups), -OH groups)
• Amino acid conjugationAmino acid conjugation
(on -COOH groups)(on -COOH groups)
• Glutathione conjugationGlutathione conjugation by Glutathione-S-transferase:by Glutathione-S-transferase:
(to epoxides or organic halides)(to epoxides or organic halides)
• Fatty acid conjugationFatty acid conjugation
(on -OH groups)(on -OH groups)
• Condensation reactionsCondensation reactions
19. 19
What the drug does to the body
- Drug receptors
- Effects of drug
- Responses to drugs
- Toxicity and adverse effects of drugs
Pharmacodynamics
Target validation
• Microarray for disease target identifi cation
• Radioligands
• High throughput screening
• Combinatorial chemistry
• Structure – activity relationships: X - ray crystallography, nuclear magnetic resonance,
computational chemistry
• Genomics and proteomics
• Metabolomics
• Systems biology
• Nanotechnology
• Bioinformatics: data mining
• Recombinant DNA technologies
23. 23
• To increase successTo increase success
• To increase bioavailabilityTo increase bioavailability
• To pass liver metabolism “First passTo pass liver metabolism “First pass
effect”effect”
• To increase Half LifeTo increase Half Life
• To increase the target to non-target uptakeTo increase the target to non-target uptake
Prodrug can be a
choice
24. 24
What is the Prodrug?
• Prodrug - a pharmacologically inactive compound that isProdrug - a pharmacologically inactive compound that is
converted to an active drug by a metabolic biotransformationconverted to an active drug by a metabolic biotransformation
(enzymatic or chemical hydrolysis)(enzymatic or chemical hydrolysis)
• Ideally,Ideally, conversion occurs as soon as the desired goal forconversion occurs as soon as the desired goal for
designing the prodrug is achieved.designing the prodrug is achieved.
• Prodrugs currently constituteProdrugs currently constitute 5%5% of known drugs and a larger percentage ofof known drugs and a larger percentage of
new drugsnew drugs
25. 25
The barriers!!!
•Low oral absorption properties
• Lack of site specificity
• Chemical instability
• Toxicity
• Bad taste
• Bad odour
• Pain at application site
27. 27
Why to use Prodrugs?
•Increased Solubility
Improve patient acceptability (decrease pain on injection)
•improve chemical stability
•minimize toxicity and side effects
•Improved Permeability and Bioavailability
Alter or improve absorption.
•Prolonged Half-Life
Alter biodistribution
Alter metabolism
elimination
Tissue-Targeted Delivery
28. 28
characteristics of prodrugs
• It should not have intrinsic pharmacologicalIt should not have intrinsic pharmacological
activity.activity.
• The prodrug must be readily transported toThe prodrug must be readily transported to
site of action.site of action.
• The prodrug must be selectively cleaved toThe prodrug must be selectively cleaved to
active drug utilizing specific enzymes.active drug utilizing specific enzymes.
32. 32
2-Bioprecursor prodrugs
It does not contain a temporary linkage between the activeIt does not contain a temporary linkage between the active
drug & a carrier moiety but designed from a moleculardrug & a carrier moiety but designed from a molecular
modification of the active principle itself.modification of the active principle itself.
It is a compound that is converted to active drug by aIt is a compound that is converted to active drug by a
Metabolic biotransformation.Metabolic biotransformation.
Types of activation-Types of activation-
OxidaOxidation (most common method)tion (most common method)
ReductionReduction
Phosphorylation (For antiviral agents)Phosphorylation (For antiviral agents)
33. 33
Oxidation Example –
Nabumetone, which is a Non-steroidal anti-inflammatory
prodrug used in arthritis
CH3
O
CH3
O
OH
CH3
O
O
series of oxidative
decaboxylation
Active form of the drug
that inhibits Prostaglandin
biosynthesis by cyclo-oxygenase
Nabumetone
34. 34
1- Carrier linked prodrug
Contain a group that can be easily removed enzymatically toContain a group that can be easily removed enzymatically to
reveal the true drugsreveal the true drugs
Ideally the group removed is pharmacologicallyIdeally the group removed is pharmacologically
inactive and nontoxic while the connecting bond must be labileinactive and nontoxic while the connecting bond must be labile
for efficient activation in vivofor efficient activation in vivo
Bipartite-Bipartite- Composed of one carrierComposed of one carrier
groupgroup attached to the drugsattached to the drugs
Tripartite-Tripartite- Carrier group is attached viaCarrier group is attached via
linker to druglinker to drug
Mutual ProdrugsMutual Prodrugs-- Two drugs linkedTwo drugs linked
togethertogether
35. 35
• Mutual prodrugMutual prodrug
• In such type of prodrug two pharmacologicallyIn such type of prodrug two pharmacologically
active agents are coupled to form a singleactive agents are coupled to form a single
molecule which acts as carrier for others.molecule which acts as carrier for others.
• Eg.benorylate is a mutual prodrug of AspirinEg.benorylate is a mutual prodrug of Aspirin
& Paracetamol.& Paracetamol.
C
O
O
NH C
O
CH3OCOCH3
COOH
OCOCH3
OH
NHCOCH3
+
prodrug
ParacetamolAsprin
Benorylate
39. 39
Prodrugs for Site Specificity (targeted therapy)
• Site specific delivery is a ultimate goal in all drug delivery research program,Site specific delivery is a ultimate goal in all drug delivery research program,
where optimal therapeutic benefit of a drug is obtained & unwanted effect arewhere optimal therapeutic benefit of a drug is obtained & unwanted effect are
minimized.minimized.
• It is desirable forIt is desirable for highly toxic compoundhighly toxic compound such as employed in a cancer.such as employed in a cancer.
• The main aim of Prodrug for Site Specificity is to achieve very precise andThe main aim of Prodrug for Site Specificity is to achieve very precise and
direct effect at the target with minimal effect on rest of the body.direct effect at the target with minimal effect on rest of the body.
• One important parameter in prodrugs for site specificity is the DrugOne important parameter in prodrugs for site specificity is the Drug
therapeutic index.therapeutic index.
A drug after its absorption into systemic circulation gets distributedA drug after its absorption into systemic circulation gets distributed intointo
target as well as non-target site.target as well as non-target site.
The distribution to non-targeted tissue may leads to undesirable toxic effectThe distribution to non-targeted tissue may leads to undesirable toxic effect
and also insufficient concentration to the target site.and also insufficient concentration to the target site.
If the target is too long and take more time for distribution the drug may getIf the target is too long and take more time for distribution the drug may get
eliminated without reaching such a site.eliminated without reaching such a site.
To minimize such a problems in a targeted drug delivery prodrug approachTo minimize such a problems in a targeted drug delivery prodrug approach
has been used.has been used.
40. 40
Novel prodrugs with modified properties has been designed
which preferentially achieve higher concentration of
biotransformed drug at the desired targeting sites such as-
Brain targeting
Kidney targeting
Liver targeting
Virus targeting
Tumor targeting
Lymphatic targeting
Colon targeting
41. 41
Targeting to brain
In a brain targeting, delivery of drug is limited by Blood Brain BarrierIn a brain targeting, delivery of drug is limited by Blood Brain Barrier
(BBB).(BBB).
The Blood Brain Barrier can allowsThe Blood Brain Barrier can allows only small and lipid solubleonly small and lipid soluble molecules,molecules,
which can diffuse the BBB from systemic circulation.which can diffuse the BBB from systemic circulation.
But the larger, more water soluble and ionic moleculesBut the larger, more water soluble and ionic molecules do notdo not readily crossreadily cross
BBB.BBB.
The BBB allows only lipophilic molecules to enter brain, on this basisThe BBB allows only lipophilic molecules to enter brain, on this basis
Bodor and Co-workers (1981) developedBodor and Co-workers (1981) developed Dihydropyridine-pyridiniumDihydropyridine-pyridinium
type redox system for Brain specific sustain drug delivery.type redox system for Brain specific sustain drug delivery.
43. 43
Targeting to Tumor
Tumor cells contains a higher concentration of enzyme
phosphates, amides than do normal cells.
Because of higher growth rates associated with tumor cells.
For tumor drug delivery firstly studied prodrug activating
enzyme (extracellular or intracellular)
For selective activation of prodrugs in tumor cells
Two steps:
Selecting a specific linker based on tumor cell specific enzyme.
Incorporate a prodrug-activating enzyme into a target tumor
cell.
44. 44
Criteria for Success With Enzyme-Prodrug Therapies
The prodrug-activating enzyme is either nonhuman or a
human protein.
It should be a good substrate for the incorporated enzyme but
not be activated by endogenous enzyme outside tumor cell.
Prodrug must be able to cross tumor cell membranes.
Prodrug have low cytotoxicity and drug have high
cytotoxicity.
The half-life of the active drug is long enough for bystander
killing effect but short enough to avoid leaking out of tumor
cells.
45. 45
Antibody targeted drugs as cancer
therapeutics
NATURE REVIEWS | DRUG DISCOVERY VOLUME 5 | FEBRUARY 2006 | 147
51. 51
Antibody-Directed Enzyme Prodrug
Therapy (ADEPT)
Administration of
Antibody-enzyme conjugate
Administration of
prodrug
Prodrug
Enzyme
Drug
Tumor cell
An approach for site-specific delivery of cancer drugs
52. 52
An antibody-enzyme conjugate is administered which
binds to the surface of the tumor cells.
The antibody used has been targeted for the particular
tumor cell.
After the antibody-enzyme has localized within the tumor
cell and the excess conjugate is cleared from the blood and
normal tissues get enough time to clear.
After the prodrug is administered, The Ab-E conjugated at
the tumor cell surface catalyzes the conversion of the
prodrug to the drug when it reaches the tumor cell.
53. 53
Example:
Delivery of Nitrogen mustard as a Glutamic acid conjugate, after
administration of humanized monoclonal antibody conjugated to
the bacterial enzyme carboxypeptidase G2.
Prodrug-activating enzyme in ADEPT is a bacterial enzyme.
I
N
I
O N
H
O
CO2
H
CO2
H
I
N
OH
I
Carboxypeptidase G2
Nitrogen mustard as a Glutamic acid conjugate Activated Nitrogen mustard
L-Glu + CO2+
54. 54
Gene-Directed Enzyme Prodrug Therapy
(GDEPT)
• An inactive prodrug can be activated to release ofAn inactive prodrug can be activated to release of
cytotoxic drug by an enzyme that has been delivered viacytotoxic drug by an enzyme that has been delivered via
gene to the tumor cell.gene to the tumor cell.
A gene encoding prodrug-activating enzyme is integratedA gene encoding prodrug-activating enzyme is integrated
into a genome of targeted tumor cells or viral vector underinto a genome of targeted tumor cells or viral vector under
the control of tumor-selective promoters.the control of tumor-selective promoters.
These cells, then express the enzyme that activates theThese cells, then express the enzyme that activates the
prodrug.prodrug.
55. 55
• Pro-prodrug (Double prodrugs)Pro-prodrug (Double prodrugs)
• Here the prodrug is further derivatised aHere the prodrug is further derivatised a
fashion such that two steps as enzymatically orfashion such that two steps as enzymatically or
chemically conversion lead to release activechemically conversion lead to release active
drug.drug.
CH C
NH2 O
NH2
S
CH3
CH3
C
O
O CH2 O C C
CH3
CH3
CH3
O
proprodrug
enzymatic clevage
S
CH3
CH3
C
O
OCH2OH
H
O
PRODRUG
N
S
CH3
CH3
O
H
Ampicillin ACTIVE
57. 57
Conclusion
• Knowing “what happened for drugs in theKnowing “what happened for drugs in the
body and how drugs act” can help a chemistbody and how drugs act” can help a chemist
to design to more effective drugsto design to more effective drugs
• Prodrug strategy increases the success ofProdrug strategy increases the success of
Drug Discovery and Development process.Drug Discovery and Development process.
58. 58
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