Transporters play an important role in drug absorption and distribution. Several computational models have been generated to predict transporter interactions and understand substrate requirements. For the P-glycoprotein transporter, models identified two hydrophobic features, two hydrogen bond acceptors, and molecular dimension as essential determinants. Breast cancer resistance protein models emphasize a double bond in ring C and hydroxylation at position 5. Organic cation transporter models found hydrogen bonding features distinguish the two orthologs.
Formulation factors affecting drug absorptionDiwakar Chudal
This document discusses how excipients and other formulation factors can influence drug absorption. It explains that excipients are added to ensure stability, uniformity, and optimal bioavailability. However, excipients can also impact absorption based on their type and amount. Factors like vehicle, diluents, binders, disintegrants and others are described in terms of how they can increase or decrease the rate of drug absorption from different dosage forms. The document emphasizes that proper selection of excipients and dosage form is important to maximize a drug's bioavailability.
This slide outlines the evaluation methods of various Controlled Drug Delivery Systems (CDDS) used in the pharmaceutical industry. The controlled Drug Delivery Systems release the drug to the plasma at a controlled, pre-determined level to ensure prolonged and adequate drug supply for a longer time. The slide analyses the various evaluation methods, its pharmacokinetic properties and applications of the evaluation methods in various scenario.
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
This document summarizes key transporters involved in drug absorption and disposition:
- Apical sodium dependent bile acid transporter (ASBT) transports bile acids and drug analogs to assist intestinal absorption, with a pharmacophore model revealing requirements of one hydrogen bond donor, one acceptor, one negative charge, and three hydrophobic centers.
- Organic cation transporters (OCTs) facilitate uptake of cationic drugs in various tissues, with a human OCT1 model suggesting requirements of three hydrophobic features and one positive ionizable feature.
- Organic anion transporting polypeptides (OATPs) influence drug plasma concentrations by transporting substrates in multiple tissues, with an OATP1B1 model identifying hydrophobic
SUSTAINED RELEASE (SR) & CONTROL RELEASE.pptxRAHUL PAL
Sustained-release medications are usually labeled with “SR” at the end of their name. These medications prolong the medication's release from a tablet or capsule so that you'll get the medication's benefits over a longer period of time.
CR = controlled release, SR = sustained release, ER = extended release, IR = immediate release. *
Transporters play an important role in drug absorption and distribution. Several computational models have been generated to predict transporter interactions and understand substrate requirements. For the P-glycoprotein transporter, models identified two hydrophobic features, two hydrogen bond acceptors, and molecular dimension as essential determinants. Breast cancer resistance protein models emphasize a double bond in ring C and hydroxylation at position 5. Organic cation transporter models found hydrogen bonding features distinguish the two orthologs.
Formulation factors affecting drug absorptionDiwakar Chudal
This document discusses how excipients and other formulation factors can influence drug absorption. It explains that excipients are added to ensure stability, uniformity, and optimal bioavailability. However, excipients can also impact absorption based on their type and amount. Factors like vehicle, diluents, binders, disintegrants and others are described in terms of how they can increase or decrease the rate of drug absorption from different dosage forms. The document emphasizes that proper selection of excipients and dosage form is important to maximize a drug's bioavailability.
This slide outlines the evaluation methods of various Controlled Drug Delivery Systems (CDDS) used in the pharmaceutical industry. The controlled Drug Delivery Systems release the drug to the plasma at a controlled, pre-determined level to ensure prolonged and adequate drug supply for a longer time. The slide analyses the various evaluation methods, its pharmacokinetic properties and applications of the evaluation methods in various scenario.
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
This document summarizes key transporters involved in drug absorption and disposition:
- Apical sodium dependent bile acid transporter (ASBT) transports bile acids and drug analogs to assist intestinal absorption, with a pharmacophore model revealing requirements of one hydrogen bond donor, one acceptor, one negative charge, and three hydrophobic centers.
- Organic cation transporters (OCTs) facilitate uptake of cationic drugs in various tissues, with a human OCT1 model suggesting requirements of three hydrophobic features and one positive ionizable feature.
- Organic anion transporting polypeptides (OATPs) influence drug plasma concentrations by transporting substrates in multiple tissues, with an OATP1B1 model identifying hydrophobic
SUSTAINED RELEASE (SR) & CONTROL RELEASE.pptxRAHUL PAL
Sustained-release medications are usually labeled with “SR” at the end of their name. These medications prolong the medication's release from a tablet or capsule so that you'll get the medication's benefits over a longer period of time.
CR = controlled release, SR = sustained release, ER = extended release, IR = immediate release. *
The document discusses the structure and function of the human gastrointestinal tract (GIT) and the mechanisms and factors affecting drug absorption through the GIT. It covers the parts and functions of the GIT, as well as the accessory organs of the liver, pancreas, and gallbladder. It then discusses the three main mechanisms of drug absorption - passive diffusion, carrier-mediated transport, and pinocytosis. Finally, it outlines various pharmaceutical and patient-related factors that can influence drug dissolution and absorption in the GIT.
Drug absorption from git , Drug absorption from git , DIGESTION AND ABSORPTION , Transcellular / intracellular , transport , .Passive Transport Processes , Passive diffusion , Pore transport , Ion- pair transport , Facilitated or mediated diffusion
, Active transport processes , Primary , Secondary , Symport (Co-transport) , Antiport (Counter transport) , Paracellular / Intercellular Transport , Permeation through tight junctions of epithelial cells , Persorption , Vesicular or Corpuscular Transport (Endocytosis) , Pinocytosis , Phagocytosis , FACTORS INFLUENCING ABSORPTION OF DRUGS , DRUG DISSOLUTION , Factors affecting dissolution rate , DISSOLUTION APPARATUS , IVIVC (In vitro- in vivo correlation) , ROLE OF DOSAGE FORM , Transport model , pH Microclimate , Intracellular pH environment , Tight junction complex
The document discusses gastrointestinal absorption of drugs. It describes the major absorption sites in the gastrointestinal tract as the stomach, small intestine, and large intestine. It then explains the various mechanisms of drug absorption including passive diffusion, carrier-mediated transport (facilitated diffusion and active transport), ionic diffusion, ion pair transport, and endocytosis. Carrier-mediated transport uses carrier proteins or enzymes to transport drugs against or along a concentration gradient. The small intestine is noted as the primary site of drug absorption due to its large surface area and longer transit time compared to other sites.
PHARMACOKINETIC AND PHARMACODYNAMIC OF BIOTEHNOLOGICAL PRODUCTSArunpandiyan59
This document discusses the pharmacokinetics and pharmacodynamics of biotechnology drugs. It begins with introducing pharmacokinetics as the study of what the body does to a drug and pharmacodynamics as the study of what a drug does to the body. It then discusses various biotechnological products including proteins, monoclonal antibodies, oligonucleotides, and vaccines. The role of pharmacokinetics and pharmacodynamics in the development of biotech drugs is explained. Key aspects like absorption, distribution, metabolism, and excretion of biotech drugs are summarized.
Review on various families of drug transporters in our body, their functions & drugs acting through them & drug interactions involving these transporters
This document discusses drug transporters and their role in drug absorption, distribution, metabolism and excretion. It covers the main types of transporters including ABC transporters like P-glycoprotein and SLC transporters. It describes how transporters regulate the movement of drugs across membranes in organs like the intestine, liver and kidneys. It also discusses how overexpression of transporters like P-glycoprotein can lead to multidrug resistance and the various approaches used to overcome resistance, such as inhibitors of transporter activity.
Dissolution and In Vitro In Vivo Correlation (IVIVC)Jaspreet Guraya
This presentation gives a bird's eye view on Dissolution in context with IVIVC. It discusses various levels of Correlations currently in practice. IVIVC are explained in light of biowaivers It also touches upon IVIVR, IVIVM etc.
Drug product performance in vivo biopharmaceuticsFeba Elsa Mathew
This document discusses drug product performance as measured by bioavailability and bioequivalence studies. It defines key terms like bioavailability, bioequivalence, absolute and relative bioavailability. Bioavailability and bioequivalence studies are used to assess drug product performance in vivo and ensure safety and efficacy. These studies are important for approval of new drug products and generic drugs to demonstrate equivalent performance.
Nucleoside transporters (NTs) are membrane proteins that transport nucleosides like adenosine across cell membranes. There are two main types: concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs). CNTs use sodium gradients to actively transport nucleosides into cells while ENTs facilitate diffusion. Both transport naturally occurring nucleosides and synthetic nucleoside drugs. Some NTs may also act as receptors that modulate cell signaling pathways. Dysregulation of NT expression is associated with various diseases including cancer and inflammatory bowel disease.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
The document discusses various transporters involved in active transport of drugs including hPEPT1, ASBT, OCT, OATP, and the BBB-choline transporter. Pharmacophore and QSAR models have been developed for many of these transporters based on in vitro data to understand their substrate binding requirements. These models can assist in predicting the effects of transporters on drug absorption, distribution, and excretion during drug development.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
This document discusses various drug transporters and how computational models have been used to better understand them. It summarizes that P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are ATP-dependent efflux transporters that impact drug absorption and resistance. The document then reviews pharmacophore and QSAR models developed for these transporters to predict substrate and inhibitor requirements. Finally, it discusses nucleoside transporters and similar computational models generated to understand these transporters and their role in drug disposition.
The brain is a delicate organ with many vital functions and many formidable mechanisms, isolate and protect it from the outside world. Unfortunately, the same mechanisms that prevent environmental chemicals accessing the brain also prevent the access of therapeutic chemicals. The brain is segregated from the circulating blood by a unique membranous barrier i.e the blood brain barrier.
This document discusses biopharmaceutical considerations and problems of variable control in dissolution testing. It addresses the importance of establishing in vitro-in vivo correlations to understand how a drug's dissolution rate relates to its absorption and bioavailability. Several factors can influence dissolution and absorption rates, including the drug's properties, dosage form characteristics, and patient factors. Understanding these relationships is important for ensuring drugs are delivered effectively to achieve their intended therapeutic effects.
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.
Drug absorption from the gastrointestinal tractSUJITHA MARY
The document discusses drug absorption from the gastrointestinal tract (GIT). It describes the key mechanisms of drug absorption including passive diffusion, carrier-mediated transport, pore transport, ionic diffusion, and vesicular transport. Factors that affect drug absorption are also covered, such as physicochemical properties like drug solubility and dissolution rate, particle size, polymorphism/amorphism, salt form, and lipophilicity. Pharmaceutical factors and patient-related factors that influence absorption are also outlined. The document provides detailed explanations of the various mechanisms and factors involved in drug absorption from the GIT.
Dissolution method and ivivc by ranjeet singhRanjeet Singh
The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
This document discusses the roles of membrane transporters in pharmacokinetics. It begins with an introduction to transporters, noting that they are membrane proteins that control the uptake and efflux of nutrients, ions, drugs and waste. Approximately 2000 human genes code for transporters. The document then covers principal sites of transporters, types of transporters including ABC transporters and SLC transporters, hepatic and renal transporters, and concludes that transporters play significant roles in drug bioavailability, efficacy and pharmacokinetics.
Protein and peptide are biopolymers which yield more than two amino acids on hydrolysis.
Although the terms ‘proteins’ and ‘peptides’ are used freely, peptides are those with molecular weight below 10,000 and proteins are molecules with higher molecular weight.
Most therapeutic proteins and peptide-based drugs are administered by parenteral route and are incorporated in liposomes to prolong their action or fused with Immunoglobulins or Albumin to improve their half-life.
PEGylation is a proven technique for improving the potentials of Proteins/peptide delivery systems.
The document discusses the structure and function of the human gastrointestinal tract (GIT) and the mechanisms and factors affecting drug absorption through the GIT. It covers the parts and functions of the GIT, as well as the accessory organs of the liver, pancreas, and gallbladder. It then discusses the three main mechanisms of drug absorption - passive diffusion, carrier-mediated transport, and pinocytosis. Finally, it outlines various pharmaceutical and patient-related factors that can influence drug dissolution and absorption in the GIT.
Drug absorption from git , Drug absorption from git , DIGESTION AND ABSORPTION , Transcellular / intracellular , transport , .Passive Transport Processes , Passive diffusion , Pore transport , Ion- pair transport , Facilitated or mediated diffusion
, Active transport processes , Primary , Secondary , Symport (Co-transport) , Antiport (Counter transport) , Paracellular / Intercellular Transport , Permeation through tight junctions of epithelial cells , Persorption , Vesicular or Corpuscular Transport (Endocytosis) , Pinocytosis , Phagocytosis , FACTORS INFLUENCING ABSORPTION OF DRUGS , DRUG DISSOLUTION , Factors affecting dissolution rate , DISSOLUTION APPARATUS , IVIVC (In vitro- in vivo correlation) , ROLE OF DOSAGE FORM , Transport model , pH Microclimate , Intracellular pH environment , Tight junction complex
The document discusses gastrointestinal absorption of drugs. It describes the major absorption sites in the gastrointestinal tract as the stomach, small intestine, and large intestine. It then explains the various mechanisms of drug absorption including passive diffusion, carrier-mediated transport (facilitated diffusion and active transport), ionic diffusion, ion pair transport, and endocytosis. Carrier-mediated transport uses carrier proteins or enzymes to transport drugs against or along a concentration gradient. The small intestine is noted as the primary site of drug absorption due to its large surface area and longer transit time compared to other sites.
PHARMACOKINETIC AND PHARMACODYNAMIC OF BIOTEHNOLOGICAL PRODUCTSArunpandiyan59
This document discusses the pharmacokinetics and pharmacodynamics of biotechnology drugs. It begins with introducing pharmacokinetics as the study of what the body does to a drug and pharmacodynamics as the study of what a drug does to the body. It then discusses various biotechnological products including proteins, monoclonal antibodies, oligonucleotides, and vaccines. The role of pharmacokinetics and pharmacodynamics in the development of biotech drugs is explained. Key aspects like absorption, distribution, metabolism, and excretion of biotech drugs are summarized.
Review on various families of drug transporters in our body, their functions & drugs acting through them & drug interactions involving these transporters
This document discusses drug transporters and their role in drug absorption, distribution, metabolism and excretion. It covers the main types of transporters including ABC transporters like P-glycoprotein and SLC transporters. It describes how transporters regulate the movement of drugs across membranes in organs like the intestine, liver and kidneys. It also discusses how overexpression of transporters like P-glycoprotein can lead to multidrug resistance and the various approaches used to overcome resistance, such as inhibitors of transporter activity.
Dissolution and In Vitro In Vivo Correlation (IVIVC)Jaspreet Guraya
This presentation gives a bird's eye view on Dissolution in context with IVIVC. It discusses various levels of Correlations currently in practice. IVIVC are explained in light of biowaivers It also touches upon IVIVR, IVIVM etc.
Drug product performance in vivo biopharmaceuticsFeba Elsa Mathew
This document discusses drug product performance as measured by bioavailability and bioequivalence studies. It defines key terms like bioavailability, bioequivalence, absolute and relative bioavailability. Bioavailability and bioequivalence studies are used to assess drug product performance in vivo and ensure safety and efficacy. These studies are important for approval of new drug products and generic drugs to demonstrate equivalent performance.
Nucleoside transporters (NTs) are membrane proteins that transport nucleosides like adenosine across cell membranes. There are two main types: concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs). CNTs use sodium gradients to actively transport nucleosides into cells while ENTs facilitate diffusion. Both transport naturally occurring nucleosides and synthetic nucleoside drugs. Some NTs may also act as receptors that modulate cell signaling pathways. Dysregulation of NT expression is associated with various diseases including cancer and inflammatory bowel disease.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
ACTIVE TRANSPORT- hPEPT1,ASBT,OCT,OATP, BBB-Choline Transporter.pptxPawanDhamala1
The document discusses various transporters involved in active transport of drugs including hPEPT1, ASBT, OCT, OATP, and the BBB-choline transporter. Pharmacophore and QSAR models have been developed for many of these transporters based on in vitro data to understand their substrate binding requirements. These models can assist in predicting the effects of transporters on drug absorption, distribution, and excretion during drug development.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
This document discusses various drug transporters and how computational models have been used to better understand them. It summarizes that P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are ATP-dependent efflux transporters that impact drug absorption and resistance. The document then reviews pharmacophore and QSAR models developed for these transporters to predict substrate and inhibitor requirements. Finally, it discusses nucleoside transporters and similar computational models generated to understand these transporters and their role in drug disposition.
The brain is a delicate organ with many vital functions and many formidable mechanisms, isolate and protect it from the outside world. Unfortunately, the same mechanisms that prevent environmental chemicals accessing the brain also prevent the access of therapeutic chemicals. The brain is segregated from the circulating blood by a unique membranous barrier i.e the blood brain barrier.
This document discusses biopharmaceutical considerations and problems of variable control in dissolution testing. It addresses the importance of establishing in vitro-in vivo correlations to understand how a drug's dissolution rate relates to its absorption and bioavailability. Several factors can influence dissolution and absorption rates, including the drug's properties, dosage form characteristics, and patient factors. Understanding these relationships is important for ensuring drugs are delivered effectively to achieve their intended therapeutic effects.
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.
Drug absorption from the gastrointestinal tractSUJITHA MARY
The document discusses drug absorption from the gastrointestinal tract (GIT). It describes the key mechanisms of drug absorption including passive diffusion, carrier-mediated transport, pore transport, ionic diffusion, and vesicular transport. Factors that affect drug absorption are also covered, such as physicochemical properties like drug solubility and dissolution rate, particle size, polymorphism/amorphism, salt form, and lipophilicity. Pharmaceutical factors and patient-related factors that influence absorption are also outlined. The document provides detailed explanations of the various mechanisms and factors involved in drug absorption from the GIT.
Dissolution method and ivivc by ranjeet singhRanjeet Singh
The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
This document discusses the roles of membrane transporters in pharmacokinetics. It begins with an introduction to transporters, noting that they are membrane proteins that control the uptake and efflux of nutrients, ions, drugs and waste. Approximately 2000 human genes code for transporters. The document then covers principal sites of transporters, types of transporters including ABC transporters and SLC transporters, hepatic and renal transporters, and concludes that transporters play significant roles in drug bioavailability, efficacy and pharmacokinetics.
Protein and peptide are biopolymers which yield more than two amino acids on hydrolysis.
Although the terms ‘proteins’ and ‘peptides’ are used freely, peptides are those with molecular weight below 10,000 and proteins are molecules with higher molecular weight.
Most therapeutic proteins and peptide-based drugs are administered by parenteral route and are incorporated in liposomes to prolong their action or fused with Immunoglobulins or Albumin to improve their half-life.
PEGylation is a proven technique for improving the potentials of Proteins/peptide delivery systems.
This document discusses proteins and peptides. It defines proteins and peptides, noting that proteins are made of 50 or more amino acids linked by peptide bonds, while peptides are shorter polymers of amino acids. The document outlines several barriers to delivering proteins and peptides as drugs, including enzymatic barriers in the gastrointestinal tract, the intestinal epithelial barrier, the capillary endothelial barrier, and the blood-brain barrier. It also describes various mechanisms of transporting peptides and proteins across these barriers, such as passive and active transport, endocytosis, and movement through tight cell junctions.
This document summarizes computational models of active transporters involved in drug disposition. It discusses models developed for P-gp, BCRP, nucleoside transporters, hPEPT1, ASBT, OCT, OATP, and the BBB choline transporter. The models were generated using techniques like pharmacophore modeling and QSAR to identify structural features important for substrate recognition and transport by each protein, which can help predict drug absorption, distribution, and excretion. The document provides details on specific structural requirements identified for several important transporters from the models.
19.los transportistas del tracto intestinal y las técnicas que se aplican par...Ever Alonso Rojas Ch
This document summarizes the main transporters expressed in the intestinal tract and techniques used to evaluate interactions between drugs and these transporters. It discusses the two major families of transporters - SLC and ABC transporters. Specific transporters discussed include P-gp, MRP2, BCRP, OCTs, OCTNs, OATPs, and PEPT1. The roles and substrates of these transporters are described. Techniques to evaluate drug-transporter interactions that are discussed include brush border membrane vesicles, everted intestinal sacs, Caco-2 cell monolayers, and in vivo methods using gene knockout animals.
Pharmacokinetics and pharmacodynamics of Biotechnological drugs-SnehalTidke
Pharmacokinetics and pharmacodynamics of biotechnological drugs along with appliations- Proteins and peptides, monoclonal antibodies, oligonucleotides, gene therapy and vaccines
primary and secondary active transport difference,Computer aided drug design P glycoprotein transport,bcrp,nt,Abst,oATP,oct,BBB choline transporter,hpepti
Barriers to Protein and peptide drug delivery system JaskiranKaur72
Protein and peptide DDS are novel systems of drug delivery.
The successful delivery of peptide and protein-based pharmaceuticals is primarily determined by its ability to cross the various barriers presented to it in the biological milieu. Various barriers encountered are-
1 Physiological Barrier
2 Intestinal Epithelial barriers
3 Capillary Endothelial Barrier
4 Blood-Brain barrier (BBB)
Drug transporters are expressed throughout the lungs and may impact the absorption and disposition of inhaled drugs. The review summarizes current knowledge on the expression and function of various drug transporters in human lungs, including ATP-binding cassette (ABC) transporters like P-glycoprotein and multidrug resistance proteins, as well as solute-linked carrier (SLC) transporters such as organic cation and anion transporters. While many transporters are expressed in lung tissue and cell lines, few studies have evaluated their impact on pulmonary drug absorption. A better understanding of drug transporters could help optimize the pharmacokinetic and pharmacodynamic profiles of inhaled medications.
The document discusses membrane transporters and their role in drug response. It begins with an overview of the major transporter superfamilies, ABC and SLC, describing their structure and function. It then examines the involvement of specific transporters in pharmacokinetic processes like hepatic and renal drug transport. The document also explores how transporters impact drug action in the brain and the relationship between transporters and both therapeutic and adverse drug responses.
Set7/9 is a lysine methyltransferase that interacts with the transcription factor Pdx1. This study found that:
1) Set7/9 methylates two lysine residues (Lys-123 and Lys-131) on Pdx1. Methylation only occurred with full-length Pdx1, indicating structural requirements.
2) Lys-131 methylation by Set7/9 augments Pdx1's transcriptional activity in luciferase reporter assays.
3) Mice with beta-cell specific deletion of Set7/9 (SetΔβ mice) showed glucose intolerance and impaired insulin secretion from islets, similar to Pdx1-deficient mice. Target genes
Drug transporters play an important role in drug absorption, distribution, metabolism, and excretion. They are located in organs like the intestine, liver, and kidney and can influence the pharmacokinetics and pharmacodynamics of drugs through drug-drug interactions. Transporters can be either uptake transporters that move drugs into cells or efflux transporters that move drugs out of cells. Inhibition or induction of these transporters by coadministered drugs can increase or decrease the intracellular concentrations of victim drugs, altering their effects. This is an important consideration for drug interactions.
Intestinal transporters in drug absorptionOmer Mustapha
This document discusses various classes of intestinal transporters involved in drug absorption. It describes Organic Anion Transporters (OATs) and Organic Anion Transporting Polypeptides (OATPs) which transport anionic drugs and are expressed in the liver and kidneys. Organic Cation Transporters (OCTs) transport cationic drugs and are expressed mainly in the liver and kidneys. Nucleoside Transporters (CNTs and ENTs) transport nucleosides and nucleoside analog drugs. Monocarboxylate Transporters (MCTs) transport short-chain fatty acids and monocarboxylates. Intestinal expression of these transporters impacts oral drug bioavailability. Understanding
This document discusses protein and peptide drug delivery. It defines proteins and describes their primary, secondary, tertiary, and quaternary structures. Proteins are classified based on structure and function. Common routes of administration for proteins and peptides include parenteral and non-parenteral routes. Parenteral routes include intravenous, intramuscular, and subcutaneous injections. Non-parenteral routes discussed are oral, nasal, buccal, ocular, rectal, and transdermal routes. Barriers to oral delivery of proteins include enzymatic degradation and lack of absorption. Strategies to overcome these barriers include chemical modification of proteins, use of absorption enhancers, and targeting specific transport mechanisms.
Artursson, Matsson, and Karlgren study in vitro models used for predicting DD...Torben Haagh
In chapter 3 of the book “Transporters in Drug Development” by B. Steffansen and A. S. Grandvuinet, the experts Artursson, Matsson, and Karlgren review in vitro characterization of DDIs with human transport proteins, in particular those that have been shown to have significant clinical effects. Read the full chapter below.
http://bit.ly/SlideshareChapter3
This document summarizes a study investigating the epigenetic changes that occur during the transdifferentiation of pancreatic acinar cells (HPACs) to hepatocyte-like cells. The study found that DNA methylation in HPACs peaks at 24 hours after treatment with dexamethasone, and the cells display phenotypic changes associated with hepatocytes after 7 days. The study also examined the promoter sequence of the SGK1 gene, which is involved in the transdifferentiation process. The results suggest therapeutic potential for producing hepatocytes from pancreatic cells to treat liver disease in a more cost-effective manner than current alternatives.
This seminar discusses computer aided drug development with a focus on efflux transporters that impact drug absorption and distribution. It describes the roles of P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), and nucleoside transporters. P-gp and BCRP are ATP-dependent efflux pumps that transport various substrates out of cells, reducing drug absorption and enhancing excretion. Inhibition of these pumps can improve drug delivery. Nucleoside transporters also transport natural and synthetic nucleoside drugs and impact their disposition. Understanding these transporters through computer modeling can help optimize drug properties.
PROTEINS: Proteins are the organic compounds made of amino acids and joined together by peptide bonds.
PEPTIDES: These are short polymers formed from the linking in a defined order of amino acids.
Protein and peptides are the most abundant material which act as hormones, transport protein, structural protein, receptor, immunoglobulin’s in living system and biological cell.
Protein and peptides are important part in several metabolic process, immunogenic defense and many other biological activities.
Protein and peptide use in the treatment of various diseases including Endocrine dysfunction, Infection diseases, Cancer, and CNS disorders.
According to their biological roles
Enzymes- Catalyses virtually all chemical reaction
Transport proteins i.e. Haemoglobin of erythrocytes
Defense proteins i.e. Immuno globulins Antibodies
Structural proteins i.e. Collagen in bones
Regulatory proteins i.e. insulin
Nutrient and storage proteins i.e. ovalbumin
According to their solubility
Globular proteins: Soluble in Water
Fibrous proteins: Insoluble in water
WHY PROTEN AND PEPTIDE DRUGS?
The protein and peptide are very important in biological cells.
Lack of proteins and peptides causes diseases like Diabetes mellitus.
Diabetes mellitus is cause due to the lack of protein called INSULIN.
Now a day R-DNA technology and hybridoma also use in protein and peptide based pharmaceuticals.
FUNCTIONS
Transport and storage of small molecules.
Coordinated motion via muscle contraction.
Mechanical support from fibrous protein.
Generation and transmission of nerve impulses.
Enzymatic catalysis.
Immune protection through antibodies.
Control of growth and differentiation via hormones.
Problems with proteins
Elimination by B and T cells.
Proteolysis by endo/exo peptidases.
Small proteins filtered out by the kidneys very quickly.
Unwanted allergic reactions may develop (even toxicity).
Loss due to insolubility/adsorption.
Protein and peptide drug delivery seminar-97-2003-final2Pravin Chinchole
The document discusses protein and peptide drug delivery. It covers the introduction to proteins and peptides, routes of absorption, properties that present challenges for delivery, and various pharmaceutical approaches to overcome these challenges. These approaches include chemical modification through prodrug approaches, use of enzyme inhibitors, penetration enhancers, and formulation vehicles like dry emulsions, microspheres, liposomes and nanoparticles. It also discusses stability aspects and recent advances in delivery of therapeutic proteins and peptides.
Physiology and chemistry of skin and pigmentation, hairs, scalp, lips and nail, Cleansing cream, Lotions, Face powders, Face packs, Lipsticks, Bath products, soaps and baby product,
Preparation and standardization of the following : Tonic, Bleaches, Dentifrices and Mouth washes & Tooth Pastes, Cosmetics for Nails.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Thinking of getting a dog? Be aware that breeds like Pit Bulls, Rottweilers, and German Shepherds can be loyal and dangerous. Proper training and socialization are crucial to preventing aggressive behaviors. Ensure safety by understanding their needs and always supervising interactions. Stay safe, and enjoy your furry friends!
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
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2. 2
Contents
Introduction
Functions
Peptide Transporter 1
Role Of Peptide Transport
Applications of PEPT 1
Regulation of Peptide Transporter
Location of peptide Transporter
2
3. Introduction
The basic mechanism is involved in solute transporter across the biological me
membrain include passive diffusion, facilited diffusion and, active transporter
Active transporter can again divided in to primary and secondary active transp
ort.
Peptides (mostly di-/tri-peptides) are normally crossed the BBB through peptid
e transporters found as an integral part of the plasma membrane proteins which
also mediate the trafficking of peptide-mimetic drugs
It should be noted that the electrochemical Na+ gradient, so-called sodium-
motive force (SMF)
The uptake and digestion of dietary proteins in the intestinal lumen are mainly
in the form of free amino acids and small peptides.
These free amino acids and small peptides absorbed are delivered to various
tissues through the blood as resources for protein synthesis and energy metabol
ites
3
4. PepT1 was first identified in 1994 as a small peptide transporter.
The complementary DNA (cDNA) encoding the human PepT1 is 2,263 base
pairs in length and has an open reading frame of 2,127 base pairs encoding 708
amino acids.
155 Up until now, two peptide transporters, namely PepT1 (SLC15A1) and Pe
pT2 (SLC15A2), have been discovered in human, which are known as proton-
coupled transporters that influx oligopeptides of 2 to 4 AAs.
Although their distributions vary from one organ to another, they are markedly
expressed by the epithelia of intestine and kidney
4
6. Functions
6
1. SLC15A1is localized to the brush border membrane of the intestinal epithelium
and mediates the uptake of di- and tripeptides from the lumen into the
enterocytes.
2. This protein plays an important role in the uptake and digestion of dietary
proteins.
3. This protein also facilitates the absorption of numerous peptidomimetic drugs.
4. mediating critical physiologic functions – important for the cellular homeostasis
of peptides and AAs.
6
7. Peptide transporter 1 (PepT 1) also known as solute carrier family 15 member 1
(SLC15A1) is a protein that in humans is encoded by SLC15A1 gene. PepT 1 is a
solute carrier for oligopeptides. It functions in renal oligopeptide reabsorption and in
the intestines in a proton dependent way, hence acting like a cotransporter.
This efflux transporter can be expressed in to gut improve drug absorption
Examples:-PEPT1,ASBT,OATP-B,OATP-D.And OATP-E.
PEPT1 Mediate the transport like peptide-like drug such as β-lactum antibiotic,
ACEIs Inhibitors the dipeptide-like anticancer drug bestatin
Peptide Transporter 1
7
8. 8
The physiological characteristics of PepT1
PepT1 is an electrogenic symporter that couples substrate and proton transport
across the cell membrane. The driving force for transport is an inwardly direct
ed -electrochemical gradient and membrane potential, which allow the substrat
es to accumulate to concentrations above the extracellular levels
8
9. Verri , Maffia , and Storelli (1992) measured accumulation in the presence of a
n inside-negative transmembrane potential in the intestinal brush-border memb
rane vesicles (BBMV) of the eel(Anguilla). Subsequently, in both herbivoro
us and carnivorous fish it was reported that intestinal transport of pep-tides is
gradient-dependent and electrogenic and sodium-independent.
9
10. Fig:-Transport of small peptides across intestinal epithelial cells. In higher
eukaryotes, the PepT family diverged into PepT1 and has a prominent expression
in intestinal epithelial cells
10
11. Molecular structure of PepT1 in fish
Based on the 20 naturally occurring amino acids, there are more than 8000 pos
sible peptides expected to be transported by PepT1,therefore has a highly prom
iscuous binding site that can accommodate a wide range of ligands with divers
e structures and chemistries. The results from multiple studies have provided a
bundant evidence for the presence of PepT1 in fish, including in vivo studies (
Bogé et al., 1981, Dabrowski et al., 2003, Dabrowski et al., 2005), in vitro assa
ys (Reshkin & Ahearn, 1991) and molecular experiments (Gonçalves et al., 20
07).Bucking and Schulte demonstrated the first functional evidence that two is
oforms of PepT1 transporters were present in fish, named SLC15A1a and SLC
15A1b.
11
12. 3-D modelling structure of Cyprinus carpio L PepT1. The structure was predicted using PyMOL .
The TM domains(transmembrane) and N- and C terminal regions are annotated.
12
13. Role and location of PEPT1 and PEPT2 transporters
PEPT1 and PEPT2 belong to the SLC transporter family and are the main pept
ide transporter within the body being responsible for the proton-coupled transp
ort of dipeptides and tripeptides. Their main function is in the absorption of di
etary nitrogen in the small intestine (PEPT1) and reabsorption of nitrogen fro
m the glomerular filtrate in the renal proximal tubule (both PEPT1 and PEPT
2).
Pathogenesis of intestinal inflammation
These transporters are also present in Brain and BBB
13
14. Firstly, localisation of PEPT1 is predominantly on the brush border of the smal
l intestine and to a lesser extent on renal epithelial cells whereas PEPT2 is wid
ely distributed in the body yet is mainly located in the renal epithelial cells.
Secondly, PEPT1 is a low affinity, high capacity transporter whereas PEPT2 is
a high affinity, low capacity transporter. Although both transporters accept a la
rge number of substrates, PEPT2 is believed to have a narrower substrate rang
e than PEPT2.
PEPT2 is widely distributed in the body and is expressed in the kidney, CNS,
and lung as well as several other tissues.
14
15. Application of PEPT1 transporter in drug delivery
PEPT1 is much more well characterised compared to PEPT2. This is in part du
e to the fact that uptake by PEPT1 is a popular route for prodrug design for dru
g delivery. For example, prodrugs which have amino acids as pro-moieties hav
e been designed as substrates of PEPT1 to improve oral absorption and bioavai
lability. The antivirals, valacyclovir and valganciclovir are examples where thi
s has been successful.
15
16. Regulation of PEPT1 transporter and its role in intestinal
inflammation
A number of factors have been reported to regulation of PEPT1 including alter
ed dietary intake and increased dietary protein. There is also evidence of the P
EPT1 transporter playing a role in the pathogenesis of intestinal inflammation
and inflammatory bowel disease. It is believed that the changes in expression o
f PEPT1 in the colon can lead to uptake of bacterial peptides. These peptides c
an activate pro-inflammatory signalling pathways leading to the release of cyto
kines and chemokines and ultimately an enhanced inflammatory response.
16
17. Location of peptide Transporter
Peptide transporters localized at brush-border membranes of intestinal a
nd renal epithelial cells mediate the membrane transport of di- and tripeptides, and
play important roles in protein absorption and the conservation of peptide-bound a
mino nitrogen.
Peptide-like drugs that show structural similarities to di- and tripeptides
are also recognized by peptide transporters.
The energy for transport of small peptides and peptide-like drugs is provided by t
he proton gradient across the cell membrane.
17
18. Membrane topology of peptide transporter 1 (PEPT1). (a) The protein contains 12 transmembr
ane domains, with the N-terminal and C-terminal ends in the cytosol. (b) Based on the analysi
s of chimeric transporters derived from PEPT1 and PEPT2, transmembrane domains in green f
orm part of the substrate-binding domain.
18
19. Case Study :-The Transport of valganciclovir, a ganciclovir pr
odrug, via peptide transporters PEPT1 and PEPT2
In clinical trials, valganciclovir, the valyl ester of ganciclovir, has been s
hown to enhance the bioavailability of ganciclovir when taken orally by patients w
ith cytomegalovirus infection. We investigated the role of the intestinal peptide tra
nsporter PEPT1 in this process by comparing the interaction of ganciclovir and val
ganciclovir with the transporter in different experimental systems. We also studied
the interaction of these two compounds with the renal peptide transporter PEPT2. I
n cell culture model systems using Caco‐2 cells for PEPT1 and SKPT cells for PE
PT2, valganciclovir inhibited glycylsarcosine transport mediated by PEPT1 and P
EPT2 with Ki values (inhibition constant) of 1.68 ± 0.30 and 0.043 ± 0.005 mM,
respectively.
19
20. The inhibition by valganciclovir was competitive in both cases. Gancicl
ovir did not interact with either transporter. Similar studies done with cloned PEP
T1 and PEPT2 in heterologous expression systems yielded comparable results. Th
e transport of valganciclovir via PEPT1 was investigated directly in PEPT1‐expres
sing Xenopus laevis oocytes with an electrophysiological approach. Valganciclovir
, but not ganciclovir, induced inward currents in PEPT1‐expressing oocytes. These
results demonstrate that the increased bioavailability of valganciclovir is related to
its recognition as a substrate by the intestinal peptide transporter PEPT1. This prod
rug is also recognized by the renal peptide transporter PEPT2 with high affinity.
20
22. Different parameters for Peptide calculation
Enter a peptide sequence using 1-letter or 3-letter amino acid codes and our peptid
e calculator will provide the following physio-chemical properties of the sequence
• Molecular weight
• Isoelectric Point
• Net charge at neutral pH(0.7)
• Average Hydrophilicity
• Ratio of hydrophilic residues to total number of residues
• Net charge Vs pH plot
• Hydrophobicity plot
22
24. Conclusion
OSR1 has the potency to downregulate the peptide transporters PEPT1 and PEPT2.
Further experiments are needed to define the in vivo significance of OSR1 sensitive p
eptide transport.
Normal human lung immunohistochemical analysis for PEPT2 protein revealed staini
ng of tracheal, bronchial, and smaller airway epithelial cells .The endothelium of smal
l vessels was also positive . The immunoreactivity was of a non-granular type and was
especially strong at the apical cellular membrane.
24
25. Reference
1]Giacomini KM, Sugiyama Y. Brunton LL, Lazo JS, Parker RL. Gilman’s The Ph
armacological Basis of Therapeutics. 2006New YorkMcGraw-Hill:41–70. This ch
apter in a textbook provides an excellent overview of transporters. 2. Schinkel AH,
Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC
) family: an overview. Adv. Drug Deliv. Rev. 2003; 55:3–29. [PubMed: 1253557
2] This manuscript provides an excellent review of ABC transporters that are impo
rtant in drug response.
3. Sai Y. Biochemical and molecular pharmacological aspects of transporters as d
eterminants of drug disposition. Drug Metab. Pharmacokinet. 2005; 20:91–99. [Pu
bMed: 15855719]
4. Cascorbi I. Role of pharmacogenetics of ATP-binding cassette transporters in th
e pharmacokinetics of drugs. Pharmacol. Ther. 2006; 112:457–473. [PubMed: 167
66035]
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26. 5. Choudhuri S, Klaassen CD. Structure, function, expression, genomic organizati
on, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MR
P), and ABCG2 (BCRP) efflux transporters. Int. J. Toxicol. 2006; 25:231–259. [Pu
bMed: 16815813]
6. Hediger MA, et al. The ABCs of solute carriers: physiological, pathological an
d therapeutic implications of human membrane transport proteins. Pflugers Arch.
2004; 447:465–468. [PubMed: 14624363]
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