Drug Transporters
Although the knowledge regarding the conduct of transporters assays and data interpretation has expanded dramatically over the past years, in vitro-to-in vivo and preclinical-to-clinical translation of transport data is still a very challenging field.
With the draft EMEA guidance, the ITC whitepaper and FDA regulation under way, performing well-designed transporter experiments has become crucial for pharmaceutical companies.
2nd congress Global Pharma Authentication 2011Torben Haagh
More at: http://www.authentication-pharma.com/web
Learn about Legislative & Regulatory Infrastructure and how to successfully use Anti-Counterfeiting technologies to reduce costs and increase your business value
The production and trade of falsified medicines has become a growing worldwide illegal business.
Für Pharmaunternehmen sind gefälschte Arzneimittel der Einnahmeverlust ein finanzielles Desaster. Unser vornehmlich englisch-sprachiger Kongress schafft eine Plattform für alle Beteiligten: von Aufsichtsbehörden, Europol bis zu Industrieexperten.
More at: http://www.authentication-pharma.com/web
Different types of Drug Transporters in body By Anubhav Singh M.pharm 1st yearAnubhav Singh
The document discusses the different mechanisms by which drugs can pass through biological barriers to reach their site of action. It describes transcellular transport, where drugs pass through cells via passive diffusion, carrier-mediated processes, or active transport. It also discusses paracellular transport between cell junctions. The main mechanisms of transcellular transport are described in detail, including passive diffusion, carrier-mediated transport, ion-pair transport, pore transport, and active transport via primary and secondary mechanisms. Vesicular transport is also summarized as a mechanism for larger molecules and particles.
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.
This document provides an overview of transporters and was prepared by Alaa Ibrahim under the supervision of Professor Sohair El Menshawy. It discusses the types, structures, mechanisms of action, regulation, physiological roles, and approaches to bypass drug transporters. The key roles of ABC and SLC transporters in drug absorption, distribution, metabolism, and excretion are summarized.
This document discusses drug transporters and their clinical importance, with a focus on P-glycoprotein. It describes two main types of drug transporters: ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporters. P-glycoprotein is an ABC transporter that transports various molecules across cell membranes in locations like the liver, kidney, placenta, and brain. It plays an important role in reducing drug absorption and access to target organs and tissues. Overexpression of P-glycoprotein can limit the effectiveness of treatments for cancer, HIV/AIDS, Alzheimer's, and epilepsy by pumping drugs back out of cells.
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 summarizes mechanisms of multidrug resistance (MDR) in organisms like bacteria and cancer cells. It discusses how MDR occurs through several mechanisms including enzymatic degradation of drugs, mutation of drug binding sites, downregulation of membrane proteins, and increased activity of efflux pumps that export drugs from cells. A major contributor to MDR is the increased expression of ATP-binding cassette (ABC) transporters like P-glycoprotein, which use ATP hydrolysis to actively transport various drugs out of cells, reducing their effectiveness. Understanding the structure and transport mechanisms of ABC transporters may help in developing new strategies to overcome MDR.
Structure and function of multidrug transporter proteins and mechanism of res...Ravinder Bhardwaj
This document discusses the structure and function of multidrug transporter proteins and the mechanism of resistance to chemotherapy. It begins by providing background on cells actively transporting compounds to maintain homeostasis. It then discusses the structure of multidrug transporters, including conserved domains, and describes both bacterial and human multidrug transporter proteins. The document focuses on ATP-binding cassette (ABC) transporters, which use ATP hydrolysis to actively transport a wide range of substrates out of cells. This efflux of drugs is the mechanism of resistance to antimicrobials and anticancer drugs.
2nd congress Global Pharma Authentication 2011Torben Haagh
More at: http://www.authentication-pharma.com/web
Learn about Legislative & Regulatory Infrastructure and how to successfully use Anti-Counterfeiting technologies to reduce costs and increase your business value
The production and trade of falsified medicines has become a growing worldwide illegal business.
Für Pharmaunternehmen sind gefälschte Arzneimittel der Einnahmeverlust ein finanzielles Desaster. Unser vornehmlich englisch-sprachiger Kongress schafft eine Plattform für alle Beteiligten: von Aufsichtsbehörden, Europol bis zu Industrieexperten.
More at: http://www.authentication-pharma.com/web
Different types of Drug Transporters in body By Anubhav Singh M.pharm 1st yearAnubhav Singh
The document discusses the different mechanisms by which drugs can pass through biological barriers to reach their site of action. It describes transcellular transport, where drugs pass through cells via passive diffusion, carrier-mediated processes, or active transport. It also discusses paracellular transport between cell junctions. The main mechanisms of transcellular transport are described in detail, including passive diffusion, carrier-mediated transport, ion-pair transport, pore transport, and active transport via primary and secondary mechanisms. Vesicular transport is also summarized as a mechanism for larger molecules and particles.
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.
This document provides an overview of transporters and was prepared by Alaa Ibrahim under the supervision of Professor Sohair El Menshawy. It discusses the types, structures, mechanisms of action, regulation, physiological roles, and approaches to bypass drug transporters. The key roles of ABC and SLC transporters in drug absorption, distribution, metabolism, and excretion are summarized.
This document discusses drug transporters and their clinical importance, with a focus on P-glycoprotein. It describes two main types of drug transporters: ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporters. P-glycoprotein is an ABC transporter that transports various molecules across cell membranes in locations like the liver, kidney, placenta, and brain. It plays an important role in reducing drug absorption and access to target organs and tissues. Overexpression of P-glycoprotein can limit the effectiveness of treatments for cancer, HIV/AIDS, Alzheimer's, and epilepsy by pumping drugs back out of cells.
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 summarizes mechanisms of multidrug resistance (MDR) in organisms like bacteria and cancer cells. It discusses how MDR occurs through several mechanisms including enzymatic degradation of drugs, mutation of drug binding sites, downregulation of membrane proteins, and increased activity of efflux pumps that export drugs from cells. A major contributor to MDR is the increased expression of ATP-binding cassette (ABC) transporters like P-glycoprotein, which use ATP hydrolysis to actively transport various drugs out of cells, reducing their effectiveness. Understanding the structure and transport mechanisms of ABC transporters may help in developing new strategies to overcome MDR.
Structure and function of multidrug transporter proteins and mechanism of res...Ravinder Bhardwaj
This document discusses the structure and function of multidrug transporter proteins and the mechanism of resistance to chemotherapy. It begins by providing background on cells actively transporting compounds to maintain homeostasis. It then discusses the structure of multidrug transporters, including conserved domains, and describes both bacterial and human multidrug transporter proteins. The document focuses on ATP-binding cassette (ABC) transporters, which use ATP hydrolysis to actively transport a wide range of substrates out of cells. This efflux of drugs is the mechanism of resistance to antimicrobials and anticancer drugs.
This document discusses drug metabolism and pharmacokinetics (DMPK). It defines DMPK as the study of what the body does to drugs (pharmacokinetics) and what drugs do to the body (pharmacodynamics). Understanding DMPK allows prediction of safe and effective drug doses. The key processes that affect drug behavior in the body are absorption, distribution, metabolism and excretion (ADME). Factors like solubility, permeability and first-pass metabolism impact drug absorption. Distribution is affected by properties like lipophilicity and plasma protein binding. Metabolism alters drugs through phases I and II to enhance excretion, and occurs mainly in the liver via cytochrome P450 enzymes. Drugs
The document discusses key aspects of new drug development and review, including discovery, preclinical and clinical testing, pharmacology studies, toxicology studies, clinical trials, and considerations for evaluating foreign clinical data to determine applicability to new populations. It emphasizes the importance of adequately characterizing pharmacokinetics, pharmacodynamics, efficacy, safety, and potential ethnic factors using well-controlled clinical trials and preclinical safety information to establish an acceptable safety profile for new drug approval.
P-glycoprotein is an ATP-binding cassette transporter that protects the body by pumping various molecules, including drugs and toxins, out of cells and preventing their accumulation. It is located on the membranes of excretory organs like the liver, kidneys, and intestines. P-gp recognizes substrates in the cell and uses ATP hydrolysis to flip them out through a central pore. Its physiological role and ability to efflux various drugs has important implications for pharmacokinetics and clinical outcomes like resistance to cancer treatments. Genetic polymorphisms in P-gp may also influence the effectiveness of drugs it transports like HIV protease inhibitors.
This document outlines an experimental research plan to characterize the ABC-G1 transporter gene in Heterobasidion annosum. The objectives are to characterize H. annosum ABCG1 genes by expressing them in yeast and validating microarray data with qRT-PCR. The methodology will involve cloning the H. annosum ABCG1 gene into a yeast expression vector, transforming yeast with the construct, and testing the yeast for terpene resistance or sensitivity. Additional experiments will validate microarray data through qPCR. Currently, researchers are tracing the ABC gene in databases and designing primers to amplify and ligate the full gene into a vector for further study.
Dokumen tersebut membahas tentang proses pembelahan sel, yang terdiri atas pembelahan amitosis, mitosis, dan meiosis. Pembelahan sel merupakan proses memperbanyak diri sel induk menjadi sel-sel anakan. Pembelahan mitosis menghasilkan sel-sel anakan yang identik dengan sel induk, sedangkan meiosis menghasilkan sel-sel gamet yang haploid untuk reproduksi seksual.
Drug transport and drug targeting - rumana hameedRumana Hameed
This document discusses genetic polymorphisms in drug transporters and drug targets. It covers various methods of targeted drug delivery including first, second, and third order targeting based on the specific cells or tissues targeted. Passive and active targeting approaches are described along with examples like magnetic drug targeting using nanoparticles, liposomes, transdermal patches, and brain-targeted delivery systems. The conclusion emphasizes that targeted drug delivery can reduce dose and side effects by assisting drugs to reach the desired site.
This document discusses two types of bisubstrate reactions: sequential or single-displacement reactions and ping-pong or double-displacement reactions. Sequential reactions involve both substrates binding to the enzyme before products are released, and can be ordered or random. Ping-pong reactions involve one substrate binding and being modified, then releasing one product before the second substrate binds and the second product is released, regenerating the original enzyme. Examples of each type of reaction are provided to illustrate the mechanisms.
This document discusses mechanisms of multi-drug resistance in bacteria and cancer cells. It describes how organisms can develop resistance through mutation, gene transfer, decreased membrane permeability, and efflux pumps that remove drugs from cells. Specifically, it explains that bacteria resist antibiotics via enzymatic degradation, altered target sites, and increased efflux. Cancer cells similarly resist chemotherapy through efflux pumps like P-glycoprotein and MDR proteins that transport drugs out of cells. The key mechanisms of multi-drug resistance shared by bacteria and cancer are efflux pumps and enzymatic deactivation of drugs.
This document discusses principles of applied pharmacokinetics in critically ill adult patients. It covers topics like why pharmacokinetics is important, the four components of pharmacokinetics (absorption, distribution, metabolism, excretion), factors affecting drug absorption like routes of administration and the gastrointestinal tract, distribution and protein binding, phases of drug metabolism, and considerations for drug dosing in renal impairment. Case examples are provided to demonstrate practical applications of pharmacokinetic principles.
Topic 4 chapter 5 part 2 enzymes - characteristics of enzymesXu Jia Xian
Enzymes have several key characteristics:
1) They speed up chemical reactions by lowering the activation energy needed.
2) They are required in minute amounts and remain unchanged after reactions.
3) They are highly specific, with each enzyme having a unique three-dimensional structure that only binds complementary substrates.
Their activity is also affected by temperature and pH - they have optimal temperatures and pH levels at which they are most active, and are deactivated outside these ranges. Some enzymes also require co-factors to function or can catalyze reversible reactions.
Pharmacokinetics :Passage of drug molecules across cell membrane and its dris...Dr.UMER SUFYAN M
The document discusses various mechanisms of drug transport across cell membranes and distribution in the body. There are four major transport mechanisms - passive diffusion, carrier-mediated transport (facilitated diffusion and active transport), pinocytosis/phagocytosis, and filtration. Passive diffusion moves drugs down a concentration gradient without energy. Carrier-mediated transport uses protein carriers and may be facilitated or active. Distribution of drugs depends on properties like lipid solubility, ionization, and protein binding. Drugs distribute to tissues, fat, bones, plasma, and other compartments before elimination from the body.
This document discusses precipitation titration, which involves the formation of an insoluble precipitate during titration. It describes the Mohr, Volhard, and Fajans methods for detecting the endpoint of precipitation titrations using different indicators like chromate, iron, and fluorescein. The Volhard method, which detects the endpoint potentiometrically by titrating excess silver with thiocyanate, is highlighted as being widely used. Limitations and ways to overcome problems of precipitation titration are also outlined.
Chapter 5 Enzymes Lesson 1 - Introduction to Enzymesj3di79
This document discusses enzymes and their roles. It defines enzymes as protein catalysts that speed up chemical reactions without being used up in the process. Enzymes work by lowering the activation energy of reactions. They are specific in what substrates they act on. The document discusses how enzymes play important roles in digestion, breaking down carbohydrates, proteins and fats into smaller molecules, as well as synthesizing complex molecules and breaking down molecules like hydrogen peroxide. Specific enzymes discussed include amylase, cellulase, proteases, lipases and catalase.
This document provides an overview of enzymes for a biology lesson. It defines enzymes as biological catalysts that are usually proteins and help speed up metabolic reactions in living organisms. It explains that enzymes work by lowering the activation energy of reactions and outlines several key points about how enzymes function, including that they have an active site that substrates bind to, and that temperature, pH, substrate concentration, and inhibitors can affect reaction rates. The objectives of the lesson are to explain enzymes, how they catalyze reactions, and factors that influence reaction rates.
Mechanisms of transport across the cell membranewaqasuk
This document discusses various mechanisms of transport across cell membranes, including:
- Passive transport mechanisms like simple diffusion, facilitated diffusion, and osmosis which do not require energy.
- Active transport mechanisms like primary and secondary active transport which move substances against their concentration gradient using cellular energy.
- Bulk transport mechanisms like filtration and vesicular transport which move larger particles and fluids across membranes.
This document discusses the four major types of adult tissues - epithelial, connective, muscle and nervous tissue. It provides details on the classification, structure and functions of each type of tissue. The key points are:
1) Tissues are classified based on structure, composition and function. The four major types are epithelial, connective, muscle and nervous tissue.
2) Epithelial tissues cover surfaces, line organs and form glands. They protect, absorb, secrete and transport. Connective tissues connect, support and protect other tissues. Muscle tissues contract to cause movement and pumping blood. Nervous tissues transmit electrical signals.
3) Each tissue contains different cell types and extracellular matrix to suit their functions.
Image and modelling for optimized translational research 2011Torben Haagh
Tool Box - Preclinical To Clinical Translation
More details can be found on: http://www.clinical-translation.de/web
Innovative methods and technologies for enhanced imaging, modelling and predictive toxicology
Preclinical to Clinical Translation - New findings on effective and safe transition from the preclinical to the clinical phase!
New efforts are needed to improve the ensemble of methods for ensuring safety and efficacy and increasing the chances of R & D to culminate in a marketable drug. And performing quality preclinical investigation is a prerequisite for reaching a decision whether to move forward towards the first-in-man study and enter phase ‘0’ of the clinical trial or not.
Der Übergang von der präklinischen zur klinischen Phase ist der entscheidende Zeitpunkt im Verlauf der Drug-Discovery. Denn noch immer scheitern 80 % der Versuche, ein Medikament zu first-in-man-studies voranzubringen. Daher wird sich die Konferenz sowohl auf diese Problematik als auch auf die vorhandenen Lösungenen im Markt konzentrieren. So wird den Teilnehmern ein breites Spektrum von Voträgen geboten, ausgehend von Einsatz innovativer Technologien im Bereich Imaging und Modelling bis hin zum intelligenten Daten Management. Entdecken Sie gemeinsam mit marktführenden Pharmaunternehmen das ideale „Werkzeug“ für erfolgsversprechende Translation!
Weiteres finden Sie auf: http://www.clinical-translation.de/web
Keywords: drug discovery, clinical trial, PBPK, PK/PD, toxicology, preclinical, clinical, translation, research, trial
7th International Conference Compound Libraries 2011Torben Haagh
More at: http://www.compound-libraries.com/web
The conference on compound libraries gives you a great insight into the latest developments and best practice solutions
In order to shorten the process, reduce costs and achieve an optimal outcome on the way to promising candidates, one must choose a smart library design from the very beginning.
Learn more on the newest and most effective library designs and screening methods in order to better manage your collections
Generating or acquiring new compound collections, successfully integrating them into an existing library and run the necessary screenings are also important aspects of the process. However, the challenges are not only technological but also organizational in nature. Today more than ever achieving hit-to-lead optimization must be interlinked with innovative outsourcing, acquisition and cooperation models.
More at: http://www.compound-libraries.com/web
This document provides information about an upcoming conference on amorphous materials to be held on May 18-19, 2010 in Ljubljana, Slovenia. The conference will explore fundamentals of amorphous forms and how to optimize commercial success with amorphous materials. Speakers will include experts from universities and pharmaceutical companies. Topics will include predicting stability, classification of materials, methods for accessing stability, and manufacturing processes. Attendees can learn practical solutions for developing amorphous drugs and gain insights from industries like biologics and food. The pre-conference workshop on May 17 will focus on analytical techniques for measuring amorphous content.
To Infinity And Beyond March 2011 Ammended For DisseminationNigel Wynne
Nigel Wynne discusses using interactive technologies like lecture capture systems, virtual patient simulations, and virtual worlds to support student engagement. He presents several case studies of technologies his research group has developed, including the Virtual Case Creator simulation platform. The technologies provide opportunities for open-ended, visual learning and better preparation for real-world skills. Evaluation of the simulations found they improved students' self-efficacy and decision-making abilities. Wynne envisions expanding these simulation-based learning approaches to other contexts.
HERE Project Interim Findings Brochure 2009Sarah_Lawther
This document summarizes interim findings from a research project on student retention and engagement in higher education. Key findings include:
1) Friendships, long term goals, personal motivation, and adapting to the course/university help students who initially consider withdrawing to ultimately stay.
2) Early information about courses and support available is important for retaining first year students. Opportunities for early social engagement also help during the transition.
3) The role of personal tutors is important in providing both academic and pastoral support for students, particularly helping them understand independent study expectations.
This document discusses drug metabolism and pharmacokinetics (DMPK). It defines DMPK as the study of what the body does to drugs (pharmacokinetics) and what drugs do to the body (pharmacodynamics). Understanding DMPK allows prediction of safe and effective drug doses. The key processes that affect drug behavior in the body are absorption, distribution, metabolism and excretion (ADME). Factors like solubility, permeability and first-pass metabolism impact drug absorption. Distribution is affected by properties like lipophilicity and plasma protein binding. Metabolism alters drugs through phases I and II to enhance excretion, and occurs mainly in the liver via cytochrome P450 enzymes. Drugs
The document discusses key aspects of new drug development and review, including discovery, preclinical and clinical testing, pharmacology studies, toxicology studies, clinical trials, and considerations for evaluating foreign clinical data to determine applicability to new populations. It emphasizes the importance of adequately characterizing pharmacokinetics, pharmacodynamics, efficacy, safety, and potential ethnic factors using well-controlled clinical trials and preclinical safety information to establish an acceptable safety profile for new drug approval.
P-glycoprotein is an ATP-binding cassette transporter that protects the body by pumping various molecules, including drugs and toxins, out of cells and preventing their accumulation. It is located on the membranes of excretory organs like the liver, kidneys, and intestines. P-gp recognizes substrates in the cell and uses ATP hydrolysis to flip them out through a central pore. Its physiological role and ability to efflux various drugs has important implications for pharmacokinetics and clinical outcomes like resistance to cancer treatments. Genetic polymorphisms in P-gp may also influence the effectiveness of drugs it transports like HIV protease inhibitors.
This document outlines an experimental research plan to characterize the ABC-G1 transporter gene in Heterobasidion annosum. The objectives are to characterize H. annosum ABCG1 genes by expressing them in yeast and validating microarray data with qRT-PCR. The methodology will involve cloning the H. annosum ABCG1 gene into a yeast expression vector, transforming yeast with the construct, and testing the yeast for terpene resistance or sensitivity. Additional experiments will validate microarray data through qPCR. Currently, researchers are tracing the ABC gene in databases and designing primers to amplify and ligate the full gene into a vector for further study.
Dokumen tersebut membahas tentang proses pembelahan sel, yang terdiri atas pembelahan amitosis, mitosis, dan meiosis. Pembelahan sel merupakan proses memperbanyak diri sel induk menjadi sel-sel anakan. Pembelahan mitosis menghasilkan sel-sel anakan yang identik dengan sel induk, sedangkan meiosis menghasilkan sel-sel gamet yang haploid untuk reproduksi seksual.
Drug transport and drug targeting - rumana hameedRumana Hameed
This document discusses genetic polymorphisms in drug transporters and drug targets. It covers various methods of targeted drug delivery including first, second, and third order targeting based on the specific cells or tissues targeted. Passive and active targeting approaches are described along with examples like magnetic drug targeting using nanoparticles, liposomes, transdermal patches, and brain-targeted delivery systems. The conclusion emphasizes that targeted drug delivery can reduce dose and side effects by assisting drugs to reach the desired site.
This document discusses two types of bisubstrate reactions: sequential or single-displacement reactions and ping-pong or double-displacement reactions. Sequential reactions involve both substrates binding to the enzyme before products are released, and can be ordered or random. Ping-pong reactions involve one substrate binding and being modified, then releasing one product before the second substrate binds and the second product is released, regenerating the original enzyme. Examples of each type of reaction are provided to illustrate the mechanisms.
This document discusses mechanisms of multi-drug resistance in bacteria and cancer cells. It describes how organisms can develop resistance through mutation, gene transfer, decreased membrane permeability, and efflux pumps that remove drugs from cells. Specifically, it explains that bacteria resist antibiotics via enzymatic degradation, altered target sites, and increased efflux. Cancer cells similarly resist chemotherapy through efflux pumps like P-glycoprotein and MDR proteins that transport drugs out of cells. The key mechanisms of multi-drug resistance shared by bacteria and cancer are efflux pumps and enzymatic deactivation of drugs.
This document discusses principles of applied pharmacokinetics in critically ill adult patients. It covers topics like why pharmacokinetics is important, the four components of pharmacokinetics (absorption, distribution, metabolism, excretion), factors affecting drug absorption like routes of administration and the gastrointestinal tract, distribution and protein binding, phases of drug metabolism, and considerations for drug dosing in renal impairment. Case examples are provided to demonstrate practical applications of pharmacokinetic principles.
Topic 4 chapter 5 part 2 enzymes - characteristics of enzymesXu Jia Xian
Enzymes have several key characteristics:
1) They speed up chemical reactions by lowering the activation energy needed.
2) They are required in minute amounts and remain unchanged after reactions.
3) They are highly specific, with each enzyme having a unique three-dimensional structure that only binds complementary substrates.
Their activity is also affected by temperature and pH - they have optimal temperatures and pH levels at which they are most active, and are deactivated outside these ranges. Some enzymes also require co-factors to function or can catalyze reversible reactions.
Pharmacokinetics :Passage of drug molecules across cell membrane and its dris...Dr.UMER SUFYAN M
The document discusses various mechanisms of drug transport across cell membranes and distribution in the body. There are four major transport mechanisms - passive diffusion, carrier-mediated transport (facilitated diffusion and active transport), pinocytosis/phagocytosis, and filtration. Passive diffusion moves drugs down a concentration gradient without energy. Carrier-mediated transport uses protein carriers and may be facilitated or active. Distribution of drugs depends on properties like lipid solubility, ionization, and protein binding. Drugs distribute to tissues, fat, bones, plasma, and other compartments before elimination from the body.
This document discusses precipitation titration, which involves the formation of an insoluble precipitate during titration. It describes the Mohr, Volhard, and Fajans methods for detecting the endpoint of precipitation titrations using different indicators like chromate, iron, and fluorescein. The Volhard method, which detects the endpoint potentiometrically by titrating excess silver with thiocyanate, is highlighted as being widely used. Limitations and ways to overcome problems of precipitation titration are also outlined.
Chapter 5 Enzymes Lesson 1 - Introduction to Enzymesj3di79
This document discusses enzymes and their roles. It defines enzymes as protein catalysts that speed up chemical reactions without being used up in the process. Enzymes work by lowering the activation energy of reactions. They are specific in what substrates they act on. The document discusses how enzymes play important roles in digestion, breaking down carbohydrates, proteins and fats into smaller molecules, as well as synthesizing complex molecules and breaking down molecules like hydrogen peroxide. Specific enzymes discussed include amylase, cellulase, proteases, lipases and catalase.
This document provides an overview of enzymes for a biology lesson. It defines enzymes as biological catalysts that are usually proteins and help speed up metabolic reactions in living organisms. It explains that enzymes work by lowering the activation energy of reactions and outlines several key points about how enzymes function, including that they have an active site that substrates bind to, and that temperature, pH, substrate concentration, and inhibitors can affect reaction rates. The objectives of the lesson are to explain enzymes, how they catalyze reactions, and factors that influence reaction rates.
Mechanisms of transport across the cell membranewaqasuk
This document discusses various mechanisms of transport across cell membranes, including:
- Passive transport mechanisms like simple diffusion, facilitated diffusion, and osmosis which do not require energy.
- Active transport mechanisms like primary and secondary active transport which move substances against their concentration gradient using cellular energy.
- Bulk transport mechanisms like filtration and vesicular transport which move larger particles and fluids across membranes.
This document discusses the four major types of adult tissues - epithelial, connective, muscle and nervous tissue. It provides details on the classification, structure and functions of each type of tissue. The key points are:
1) Tissues are classified based on structure, composition and function. The four major types are epithelial, connective, muscle and nervous tissue.
2) Epithelial tissues cover surfaces, line organs and form glands. They protect, absorb, secrete and transport. Connective tissues connect, support and protect other tissues. Muscle tissues contract to cause movement and pumping blood. Nervous tissues transmit electrical signals.
3) Each tissue contains different cell types and extracellular matrix to suit their functions.
Image and modelling for optimized translational research 2011Torben Haagh
Tool Box - Preclinical To Clinical Translation
More details can be found on: http://www.clinical-translation.de/web
Innovative methods and technologies for enhanced imaging, modelling and predictive toxicology
Preclinical to Clinical Translation - New findings on effective and safe transition from the preclinical to the clinical phase!
New efforts are needed to improve the ensemble of methods for ensuring safety and efficacy and increasing the chances of R & D to culminate in a marketable drug. And performing quality preclinical investigation is a prerequisite for reaching a decision whether to move forward towards the first-in-man study and enter phase ‘0’ of the clinical trial or not.
Der Übergang von der präklinischen zur klinischen Phase ist der entscheidende Zeitpunkt im Verlauf der Drug-Discovery. Denn noch immer scheitern 80 % der Versuche, ein Medikament zu first-in-man-studies voranzubringen. Daher wird sich die Konferenz sowohl auf diese Problematik als auch auf die vorhandenen Lösungenen im Markt konzentrieren. So wird den Teilnehmern ein breites Spektrum von Voträgen geboten, ausgehend von Einsatz innovativer Technologien im Bereich Imaging und Modelling bis hin zum intelligenten Daten Management. Entdecken Sie gemeinsam mit marktführenden Pharmaunternehmen das ideale „Werkzeug“ für erfolgsversprechende Translation!
Weiteres finden Sie auf: http://www.clinical-translation.de/web
Keywords: drug discovery, clinical trial, PBPK, PK/PD, toxicology, preclinical, clinical, translation, research, trial
7th International Conference Compound Libraries 2011Torben Haagh
More at: http://www.compound-libraries.com/web
The conference on compound libraries gives you a great insight into the latest developments and best practice solutions
In order to shorten the process, reduce costs and achieve an optimal outcome on the way to promising candidates, one must choose a smart library design from the very beginning.
Learn more on the newest and most effective library designs and screening methods in order to better manage your collections
Generating or acquiring new compound collections, successfully integrating them into an existing library and run the necessary screenings are also important aspects of the process. However, the challenges are not only technological but also organizational in nature. Today more than ever achieving hit-to-lead optimization must be interlinked with innovative outsourcing, acquisition and cooperation models.
More at: http://www.compound-libraries.com/web
This document provides information about an upcoming conference on amorphous materials to be held on May 18-19, 2010 in Ljubljana, Slovenia. The conference will explore fundamentals of amorphous forms and how to optimize commercial success with amorphous materials. Speakers will include experts from universities and pharmaceutical companies. Topics will include predicting stability, classification of materials, methods for accessing stability, and manufacturing processes. Attendees can learn practical solutions for developing amorphous drugs and gain insights from industries like biologics and food. The pre-conference workshop on May 17 will focus on analytical techniques for measuring amorphous content.
To Infinity And Beyond March 2011 Ammended For DisseminationNigel Wynne
Nigel Wynne discusses using interactive technologies like lecture capture systems, virtual patient simulations, and virtual worlds to support student engagement. He presents several case studies of technologies his research group has developed, including the Virtual Case Creator simulation platform. The technologies provide opportunities for open-ended, visual learning and better preparation for real-world skills. Evaluation of the simulations found they improved students' self-efficacy and decision-making abilities. Wynne envisions expanding these simulation-based learning approaches to other contexts.
HERE Project Interim Findings Brochure 2009Sarah_Lawther
This document summarizes interim findings from a research project on student retention and engagement in higher education. Key findings include:
1) Friendships, long term goals, personal motivation, and adapting to the course/university help students who initially consider withdrawing to ultimately stay.
2) Early information about courses and support available is important for retaining first year students. Opportunities for early social engagement also help during the transition.
3) The role of personal tutors is important in providing both academic and pastoral support for students, particularly helping them understand independent study expectations.
Assessing innovation of end-of-life treatments appraised by NICEHTAi Bilbao 2012
1. The document summarizes a study that explored how NICE recognizes innovation in end-of-life treatments through its guidance.
2. The results showed that treatments recommended by NICE had higher median and mean survival benefits compared to those not recommended, as well as longer patient life expectancies and durations of survival data available.
3. Key factors in NICE's decisions appeared to be the base case ICER, additional patient life expectancy provided by the treatment, and additional survival benefit relative to existing treatments.
2. 12th – 14th April 2011 | Maritim pro Arte Berlin
Dear colleague, Sponsorship
Since IQPC's first meeting on clinically relevant drug transporters in 2009 considerable progress has been We have a variety of packages
made in understanding the influence of membrane transporters on drug absorption, disposition, metabo- available to suit your requirements.
lism and elimination. Although the knowledge regarding the conduct of transporters assays and data inter- For all Sponsorship and Exhibition
pretation has expanded dramatically over the past years, in vitro-to-in vivo and preclinical-to- opportunities call Neil Corteen:
clinical translation of transport data is still a very challenging field. +49 (0)30 20 91 32 75 or email
neil.corteen@iqpc.de.
With the draft EMEA guidance, the ITC whitepaper and FDA regulation under way, performing well-designed
transporter experiments has become crucial for pharmaceutical companies.
So don´t miss IQPC's second conference
For further information
CliniCally relevant drug transporters please visit our website
www.drug-transporters.com/SP or
Mechanistic modelling of transporter driven PK – Drug-drug interaction – contact Brijesh Patel on
Translation of transport data +49 (0)30 20 91 33 33 or email
brijesh.patel@iqpc.de.
12th – 14th April 2011 | Maritim pro Arte Berlin
which will bring together pharmaceutical and academic scientists. Areas of discussion will include:
Team Discounts
• Effective testing and modelling methodology We are offering attractive Team
• In vitro-to-in vivo and preclinical-to-clinical translation of transport data Discounts, please contact us!
• Impact of regulatory authorities and the ITC whitepaper
We are looking forward to meeting you in Berlin.
Kind regards
Sebastian Krzonkalla
Product Manager
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To Register | T +49 (0)30 20 91 33 33 | F +49 (0)30 20 91 32 10 | E brijesh.patel@iqpc.de | www.drug-transporters.com/SP
3. CoNFERENCE DAy oNE | Tuesday, 12th April 2011
09:00 Registration & coffee 13:15 Networking luncheon
09:30 Chairman´s welcome and opening address 14:15 Glial Cells: Secondary Barriers to Drug Permeability
H
ig
hl
Ph.D. Maarten T. Huisman, • Contribution of glial cells to the neurovascular unit
ig
ht
DMPK Belgium, Teamleader PK-lab Belgium & Leader barrier function
J&J Center of Expertise Transporters, • Localization and functional expression of ATP-Binding
Johnson & Johnson, Belgium Cassette (ABC) membrane transporters in glial cells
(astrocytes and microglia)
Absorption • Regulation of ABC transporters by HIV viral coat protein,
gp-120, in glial cells, a cellular target of HIV infection
09:45 The influence of drug transporters on drug absorption • Complexity of drug-transporter interactions in the
• Relevant transporters in the gut context of HIV-associated inflammation and oxidative stress
• uptake transporters Ph.D. Reina Bendayan,
• Efflux Transporters Professor and Associate Dean, Graduate Education,
Ph.D. Sven Stegemann, Department of Pharmaceutical Sciences, Leslie Dan
Director Global Pharmaceutical Business Development Faculty of Pharmacy,
Capsugel, Division of Pfizer, Belgium University of Toronto, Canada
Distribution / Metabolism / Elimination 15:00 Impact of regulatory authorities and the ITC Whitepaper
• Impact of FDA regulation
• Impact of ITC Whitepaper
10:30 Human uptake and efflux transporters and their role in
• Interpretation and application of the draft EMEA
hepatic drug absorption, metabolism, and elimination –
guidance
Focus on lIvER
• Japan
• Relevance of transport proteins for drug half-life, uptake,
Dr. Dietmar Weitz,
and action
Laboratory Head, MPK Metabolism & In vitro Systems,
• Drug uptake into human hepatocytes by OCT and OATP
Sanofi-Aventis Deutschland GmbH, Germany
proteins
• Drug efflux into bile / into the circulation by efflux
15:45 Refreshment break & networking
transporters (e.g. MRP2, MRP4, MDR1 P-glycoprotein)
• In vitro systems to measure uptake and efflux
transporters Transporters & Toxicity
• Pharmacogenetics of drug transporters
PD Dr. Anne Nies,
16:15 Renal organic anion transporters: Is regulation of
Head Membrane Transport Proteins,
expression involved in renal damage after ischemia?
Dr. Margarete Fischer-Bosch Institute of Clinical
• OAT1 (Slc22a6)
Pharmacology, Stuttgart
• OAT3 (Slc22a8)
University of Tübingen, Germany
• Regulation of expression
11:15 Refreshment break & networking • Renal ischemia and reperfusion
• Renal outcome
11:45 Focus on KIDNEy PD Dr. Christoph Sauvant,
H
ig
Role of organic ion transporters in the renal elimination Laboratory Head,
hl
ig
of drugs: clinical investigation using in vivo inhibitors
ht
University Halle-Wittenberg, Germany
• In vivo inhibitors for OAT1, OAT3, MATE1 and MATE2-K
• In vitro evaluation of transporter function using human 17:00 Closing remarks of the chairman
kidney slices and brush border membrane vesicles and end of conference day one
• Drug-drug interaction studies using probe substrates and
inhibitors in healthy subjects
• Endogenous substrates of renal organic ion transporters
Dr. Hiroyuki Kusuhara,
Associate Professor Department of Molecular PK,
University of Tokyo, Japan
12:30 Drug Transport across the Blood-Brain Barrier (BBB)
• Structure and function of the BBB
• Regulation and Modulation of transporters
• Models of the BBB
• Drug Delivery Systems for CNS-delivery
Prof. Dr. Gert Fricker,
Director at the Institute of Pharmacy and Molecular
Biotechnology,
University of Heidelberg, Germany
To Register | T +49 (0)30 20 91 33 33 | F +49 (0)30 20 91 32 10 | E brijesh.patel@iqpc.de | www.drug-transporters.com/SP
4. CoNFERENCE DAy TWo | Wednesday, 13th April 2011
08:30 Registration & coffee James Clarke,
Scientist, DMPK,
09:00 Chairman´s welcome and opening address GlaxoSmithKline R&D, UK
Ph.D. Sven Stegemann,
Director Global Pharmaceutical Business Development 13:00 Networking luncheon
Capsugel, Division of Pfizer, Belgium
14:00 Interplay of Metabolism and Transport in Determining
oral Drug Absorption and Gut Wall Metabolism:
Mechanistic Modelling of Transporter Driven PK & DDI
A Simulation Assessment Using the “Advanced
Dissolution, Absorption, Metabolism (ADAM)” Model
09:15 Introduction into in vitro / in vivo models Amin Rostami-Hodjegan, Professor of Systems
H
ig
• Overview of key in vitro / in vivo tools
hl
Pharmacology,
ig
• Advantages/Disadvantages
ht
School of Pharmacy and Pharmaceutical Sciences
• IVIVC
University of Manchester
Ph.D. Maarten T. Huisman,
Director of Scientific Development,
DMPK Belgium, Teamleader PK-lab Belgium & Leader
J&J Center of Expertise Transporters, Simcyp limited Blades Enterprise Centre
Johnson & Johnson, Belgium
14:45 Development of a novel human proximal tubule cell
Laurent Salphati, model to understand the renal handling of drug molecules
Scientist, • We have developed a fully differentiated Human primary
Genentech Inc., Member of the Roche Group, USA proximal tubule cell model
• Cell monolayers exhibit vectorial transport of key
10:45 Refreshment break & networking prototypic substrates
• We can quantify the contribution of individual
11:15 Transporter Pharmacoproteomics: Protein
H
transporters to the handling of drug molecules
ig
quantification for nonclinical and clinical research in
hl
ig
the industry and the hospital • We can identify key sites of drug-drug interactions
ht
• Introduction: Why transporter protein quantification is • We can study transporter expression and function in
important ? response to substrate exposure
• Methodology: How to quantify transporter protein by LC- Dr Colin D A Brown Ph.D, Epithelial Research Group
MS/MS ? (Detection limit, dynamic range, reproducibility) Institute for Cell & Molecular Bioscience,
• Application Medical School, Newcastle University
Quantitative evaluation of in vitro culture system
based on the transporter protein quantification 15:30 Refreshment break & networking
Quantitative evaluation of in vivo animal model based
on the transporter protein quantification in mouse,
16:00 Modelling of Transporter Driven DDI
monkey and human
Reconstruction of in vivo brain distribution for several • uptaketransporter and exportpumps relevant for DDI
drugs based on the mdr1a/MDR1 protein • hepatic and renal Transporters
quantification at the BBB • In vitro analysis of DDIs
Reconstruction of in vivo brain drug distribution in the • In vivo relevance of DDIs
diseased animal model based on the mdr1a/MDR1 PD Dr. Jörg König,
protein quantification at the BBB Institute of Experimental and Clinical Pharmacology
Quantitative evaluation of drug efflux transporters in and Clinical Toxicology,
the malignant glioblastoma and metastatic brain tumor Friedrich-Alexander-University Erlangen-Nürnberg,
patients based on the transporter protein quantification
Germany
• Perspective
Ph.D. Tetsuya Terasaki, Distinguished Professor,
Division of Membrane Transport and Drug Targeting 16:45 Transporter investigations to explain mechanisms of
Department of Biochemical Pharmacology and clinical DDIs
Therapeutics, Graduate School of Pharmaceutical • Astrazeneca drug development cases
Sciences, • Application of assays for uptake and efflux transporters
Tohoku University • Preclinical-to-clinical translation of transporter data
Johan Palm, PhD,
12:15 The mechanistic understanding and prediction of renal Clinical Pharmacology & DMPK, Mölndal,
drug-drug interactions with methotrexate: An industry AstraZeneca R&D Mölndal, Sweden
perspective
• An introduction to the PK and ADME of methotrexate
17:30 outlook Transporters
(with a focus on transporter mediated disposition)
• Methotrexate drug-drug interactions, a mechanistic Ph.D. Maarten T. Huisman,
understanding DMPK Belgium, Teamleader In Vitro Lab DMPK Belgium
• Prediction of methotrexate drug-drug interactions using and Leader J&J´s Center of Expertise Transporters,
in-vitro data from organic anion transporter assays Johnson & Johnson, Belgium
• Gaps in our knowledge around methotrexate drug-drug
interaction and how this is being addressed (includes 17:45 Closing remarks of the chairman
PBPK modelling efforts) and end of conference day two
To Register | T +49 (0)30 20 91 33 33 | F +49 (0)30 20 91 32 10 | E brijesh.patel@iqpc.de | www.drug-transporters.com/SP
5. INTERACTIvE WoRKSHoP DAy | Thursday, 14th April 2011
Workshop A
09:00 – 12:00
Neurovascular Unit and Biochemical Barrier Function
Limited drug penetration is an obstacle that is often encountered in the treatment of CNS diseases including human immuno-
deficiency virus type-1 (HIV-1) encephalitis (HIVE) and brain tumors. One mechanism that may contribute to this phenomenon is
the expression of ATP-binding cassette (ABC) drug efflux transporters [i.e., P-glycoprotein (P-gp), Multidrug Resistance-Associated
Proteins (MRPs/Mrps), Breast Cancer Resistance Protein (BCRP; also known as ABCG2)] at the blood-brain barrier (BBB). We
have demonstrated that ABC transporters are not only expressed in brain microvessel endothelial cells which form the BBB but
also in glial cells, the primary target of HIV infection in the brain. We propose that the localisation of these transporters in brain
parenchyma may also contribute to the low accumulation and altered distribution of several therapeutic compounds including
antiretroviral drugs and chemotherapeutic agents in the brain by creating a “secondary barrier” This workshop will discuss the
.
potential contribution of glial cells to the neurovascular unit barrier function and drug resistance in the context of HIV infection and
cancer.
Ph.D. Reina Bendayan, Professor and Associate Dean, Graduate Education Department of Pharmaceutical Sciences,
Leslie Dan Faculty of Pharmacy, University of Toronto, Canada
Workshop B
09:00 – 12:00
ABC of Modelling Transporter Data (I) - Principles and Practical Know How
The session will give a step-by-step guide to enable participants in understanding the terms applied within modelling are-
ana as applied to transporters. Transporter related experiments will be revisited and pitfalls will be highlighted to assist the
researchers in finding their way through the complex datasets obtained via various in vitro techniques. All participants will
have the opportunity of experiencing interactive problem solving sessions facilitated by experienced tutors.
Workshop Lead:
Amin Rostami-Hodjegan, Professor of Systems Pharmacology, School of Pharmacy and Pharmaceutical Sciences
University of Manchester, UK
Director of Scientific Development, Simcyp limited Blades Enterprise Centre, UK
Worksop Tutors:
Mr Matthew Harwood and Dr Fania Bajot, Research Scientists, Simcyp limited, Sheffield, UK
Workshop C ABC of Modelling Transporter Data (II) - Applications and Combining In vitro Knowledge
13:00 – 16:00 with Clinical observations
The session deals in details with complexity of the models related to transporters in gut and liver. The session touches
upon transporter modelling in brain and kidneyi before desending to practical examples involving the applications of the
modelling approach to answer observations related to oral bioavailability, hepatic clearance, drug-drug interactions (DDIs),
and drug distribution to different organs. Impact of population variability and approaches to handling genetic variations are
also discussed.
Workshop Lead:
Amin Rostami-Hodjegan, Professor of Systems Pharmacology, School of Pharmacy and Pharmaceutical Sciences
University of Manchester, UK
Director of Scientific Development, Simcyp limited Blades Enterprise Centre, UK
Worksop Tutors:
Mr Matthew Harwood and Dr Fania Bajot, Research Scientists, Simcyp limited, Sheffield, UK
Workshop D Species differences in drug transport and drug metabolism - do we have good enough
13:00 – 16:00 experimental models to work with?
What technologies should we be thinking of developing?
• Humanised animal models
• Computer PK-PD models
• Primary in-vitro human cell models ( hepatocyte sandwich, proximal tubule monolayers)
• Stem cell derived models?
Dr Colin D A Brown Ph.D, Epithelial Research Group, Institute for Cell & Molecular Bioscience, Medical School,
Newcastle University
To Register | T +49 (0)30 20 91 33 33 | F +49 (0)30 20 91 32 10 | E brijesh.patel@iqpc.de | www.drug-transporters.com/SP