Download or read book Role of Membrane Transporters in Drug Delivery Drug Disposition and Drug drug Interactions written by Varun Khurana and published by . This book was released on 2014 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Drug Transporters written by Glynis Nicholls and published by Royal Society of Chemistry. This book was released on 2016 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. In this first volume on Drug Transporters, the current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics are comprehensively reviewed. The second volume of the book is specifically dedicated to emerging science and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.
Download or read book Fundamentals of Drug Delivery written by Heather A. E. Benson and published by John Wiley & Sons. This book was released on 2021-10-12 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive guide to the current research, major challenges, and future prospects of controlled drug delivery systems Controlled drug delivery has the potential to significantly improve therapeutic outcomes, increase clinical benefits, and enhance the safety of drugs in a wide range of diseases and health conditions. Fundamentals of Drug Delivery provides comprehensive and up-to-date coverage of the essential principles and processes of modern controlled drug delivery systems. Featuring contributions by respected researchers, clinicians, and pharmaceutical industry professionals, this edited volume reviews the latest research in the field and addresses the many issues central to the development of effective, controlled drug delivery. Divided in three parts, the book begins by introducing the concept of drug delivery and discussing both challenges and opportunities within the rapidly evolving field. The second section presents an in-depth critique of the common administration routes for controlled drug delivery, including delivery through skin, the lungs, and via ocular, nasal, and otic routes. The concluding section summarizes the current state of the field and examines specific issues in drug delivery and advanced delivery technologies, such as the use of nanotechnology in dermal drug delivery and advanced drug delivery systems for biologics. This authoritative resource: Covers each main stage of the drug development process, including selecting pharmaceutical candidates and evaluating their physicochemical characteristics Describes the role and application of mathematical modelling and the influence of drug transporters in pharmacokinetics and drug disposition Details the physiology and barriers to drug delivery for each administration route Presents a historical perspective and a look into the possible future of advanced drug delivery systems Explores nanotechnology and cell-mediated drug delivery, including applications for targeted delivery and toxicological and safety issues Includes comprehensive references and links to the primary literature Edited by a team of of internationally-recognized experts, Fundamentals of Drug Delivery is essential reading for researchers, industrial scientists, and advanced students in all areas of drug delivery including pharmaceutics, pharmaceutical sciences, biomedical engineering, polymer and materials science, and chemical and biochemical engineering.
Download or read book Drug Transporters written by Guofeng You and published by John Wiley & Sons. This book was released on 2022-04-06 with total page 1269 pages. Available in PDF, EPUB and Kindle. Book excerpt: DRUG TRANSPORTERS Drug transporter fundamentals and relevant principles and techniques, featuring new and expanded chapters Drug Transporters: Molecular Characterization and Role in Drug Disposition provides in-depth analysis of the conceptual evolution and technical development for studying drug transporters. Contributions by an international panel of leading researchers address advances in transporters as drug targets, transporters in pharmacotherapy, the impact of transporters on drug efficacy and safety, the development of sophisticated model systems and sensitive assay methods, and more. Divided into two parts, the book first provides a thorough overview of relevant drug transporters before detailing the principles of drug transport and associated techniques. The updated and expanded third edition includes new chapters on in vitro-in vivo scale-up of drug transport activities, the ontogeny of drug transporters, the application of physiologically-based pharmacokinetic and pharmacodynamic modeling, and the use of transporters as therapeutic targets for diseases. Reflects the current state of the field and offers perspectives on future directions Covers basic knowledge, clinical outcomes, and emerging discoveries in transporter science Provides up-to-date information on drug transporter families, mechanisms, and clinical implications Includes extensive references and numerous figures and tables throughout Understandable for novices while offering sufficient depth for more experienced researchers, Drug Transporters: Molecular Characterization and Role in Drug Disposition, Third Edition is an excellent textbook for pharmacological or physiological science courses in drug/membrane transport, and an invaluable reference for academic or industrial scientists working in the transporter field and related areas of drug metabolism, pharmacokinetics, and pharmacodynamics.
Download or read book Drug Transporters in Drug Disposition Effects and Toxicity written by Xiaodong Liu and published by Springer Nature. This book was released on 2019-09-30 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides with a comprehensive overview of the role of drug transporters in drug disposition and efficacy/toxicity, as well as drug-drug interactions and recent advances in the field. Transporters are known determinants of drug disposition and efficacy/toxicity. In general, they are divided into solute carrier (SLC) and ATP binding cassette (ABC) families, and are located along cell membranes, where they mediate drug uptake into cells and export out of cells. Drug transporters are essential in maintaining cell homeostasis, and their gene mutations may cause or contribute to severe human genetic disorders, such as cystic fibrosis, neurological disease, retinal degeneration, anemia, and cholesterol and bile transport defects. Conversely, some diseases may also alter transporter functions and expressions, in turn aggravating disease process. Further, since over-expression of some ABC transporters is a potential contributor to multidrug-resistance (MDR), the book presents a number of strategies to overcome MDR, including ABC transporter inhibitors and applying epigenetic methods to modulate transporter expressions and functions. This book is useful for graduate students and professionals who are looking to refresh or expand their knowledge of this exciting field.
Download or read book Drug Transporters written by Glynis Nicholls and published by Royal Society of Chemistry. This book was released on 2016-08-16 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. In this first volume on Drug Transporters, the current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics are comprehensively reviewed. The second volume of the book is specifically dedicated to emerging science and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.
Download or read book Membrane Transporters and Channels as Targets for Drugs written by Graça Soveral and published by Frontiers Media SA. This book was released on 2020-01-03 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.
Download or read book Transporters in Drug Development written by Yuichi Sugiyama and published by Springer Science & Business Media. This book was released on 2013-09-16 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters in Drug Development examines how membrane transporters can be dealt with in academic–industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters’ impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process.
Download or read book Drug Transporters written by Martin F. Fromm and published by Springer Science & Business Media. This book was released on 2010-11-19 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.
Download or read book Drug Transporters written by Guofeng You and published by John Wiley & Sons. This book was released on 2014-07-07 with total page 1012 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new edition overviews drug transporters and presents the principles of drug transport and associated techniques, featuring new chapters on multidrug and toxin extrusion proteins, placental transport, in silico approaches in drug discovery, and regulatory guidance for drug transport studies in drug development. • Describes drug transporter families, mechanisms, and clinical implications along with experimental methods for studying and characterizing drug transporters • Includes new chapters on multidrug and toxin extrusion proteins, placental transport and in silico approaches in drug discovery • Has a new chapter covering regulatory guidance for the evaluation of drug transport in drug development with global criteria used for drug transporters in clinical trials • Arranges material to go from fundamental mechanisms to clinical outcomes, making the book useful for novice and expert readers
Download or read book Membrane Transporters as Drug Targets written by Gordon L. Amidon and published by Springer Science & Business Media. This book was released on 2006-04-11 with total page 547 pages. Available in PDF, EPUB and Kindle. Book excerpt: Because progress in the field of transporters has been extraordinary, this volume will focus on recent advances in our understanding of the structure, function, physiology, and molecular biology of membrane transporters. There will be an emphasis on transporters as molecular targets for drug delivery and disposition in the body.
Download or read book Enzyme Kinetics in Drug Metabolism written by Swati Nagar and published by Humana. This book was released on 2014-02-13 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug metabolism and transport are very important facets within the discipline of pharmaceutical sciences, with enzyme kinetic concepts utilized regularly in characterizing and modeling the disposition and elimination of drugs. Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications focuses on very practical aspects of applying kinetic principles to drug metabolizing enzymes and transporters. Divided into five convenient sections, topics include the fundamental principles of enzyme kinetics, the kinetics of oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for both drug metabolizing enzymes and transporters including novel systems biology approaches, understanding of variability both experimental and interindividual (pharmacogenomic), and case studies that provide real life examples of applying these principles. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics especially suitable for the novice, in some cases step-by-step, readily reproducible protocols, and insights to help with troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and easily accessible, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications serves as a very practical teaching tool for novice, non-mathematically trained scientists interested in these fundamental concepts and as an aid for their supervisors in teaching these principles.
Download or read book Enzyme and Transporter Based Drug Drug Interactions written by K. Sandy Pang and published by Springer Science & Business Media. This book was released on 2009-12-17 with total page 742 pages. Available in PDF, EPUB and Kindle. Book excerpt: Germination of the thought of "Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges" Proceedings came about as part of the annual meeting of The American Association of Pharmaceutical Scientists (AAPS) that was held in San Diego in November of 2007. The attendance of workshop by more than 250 pharmaceutical scientists reflected the increased interest in the area of drug-drug interactions (DDIs), the greater focus of PhRMA, academia, and regulatory agencies, and the rapid pace of growth in knowledge. One of the aims of the workshop was to address the progress made in quantitatively predicting enzyme- and transporter-based DDIs as well as highlighted areas where such predictions are poor or areas that remain challenging for the future. Because of the serious clinical implications, initiatives have arisen from the FDA (http://www.fda.gov/cber/gdlns/interactstud.htm) to highlight the importance of enzyme- and transporter-based DDIs. During the past ten to fifteen years, we have come to realize that transporters, in addition to enzymes, play a vital role in drug elimination. Such insight has been possible because of the continued growth in PK-ADME (pharmacokinetics-absorption-distribution-metabolism-excretion) knowledge, fueled by further advances in molecular biology, greater availability of human tissues, and the development of additional and sophisticated model systems and sensitive assay methods for studying drug metabolism and transport in vitro and in vivo. This has sparked an in-depth probing into mechanisms surrounding DDIs, resulting from ligand-induced changes in nuclear receptors, as well as alterations in transporter and enzyme expression and function. Despite such advances, the in vitro and in vivo study of drug interactions and the integration of various data sets remain challenging. Therefore, it has become apparent that a proceeding that serves to encapsulate current strategies, approaches, methods and applications is necessary. As Editors, we have assembled a number of opinion leaders and asked them to contribute chapters surrounding these issues. Many of these are the original Workshop speakers whereas others had been selected specially to contribute on topics related to basic and applied information that had not been covered in other reference texts on DDI. The resulting tome, entitled Enzyme- and Transporter-Based Drug Interactions: Progress and Future Challenges, comprises of four sections. Twenty-eight chapters covering various topics and perspectives related to the subject of metabolic and transporter-based drug-drug interactions are presented.
Download or read book Oral Drug Absorption written by Jennifer B. Dressman and published by CRC Press. This book was released on 2016-04-19 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an
Download or read book Drug Transporters written by Glynis Nicholls and published by Royal Society of Chemistry. This book was released on 2016-08-17 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding and quantifying the effects of membrane transporters within the human body is essential for modulating drug safety and drug efficacy. The first volume comprehensively reviewed current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics. In this second volume on Drug Transporters, emphasis is placed on emerging sciences and technologies, highlighting potential areas for future advances within the drug transporter field. The topics covered in both volumes ensure that all relevant aspects of transporters are described across the drug development process, from in silico models and preclinical tools through to the potential impact of transporters in the clinic. Contributions are included from expert leaders in the field, at-the-bench industrial scientists, renowned academics and international regulators. Case studies and emerging developments are highlighted, together with the merits and limitations of the available methods and tools, and extensive references to reviews on specific in-depth topics are also included for those wishing to pursue their knowledge further. As such, this text serves as an essential handbook of information for postgraduate students, academics, industrial scientists and regulators who wish to understand the role of transporters in absorption, distribution, metabolism, and excretion processes. In addition, it is also a useful reference tool on the models and calculations necessary to predict their effect on human pharmacokinetics and pharmacodynamics.
Download or read book Transporters in Drug Discovery and Development written by Yurong Lai and published by Woodhead Publishing. This book was released on 2014-08-22 with total page 759 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by a leading researcher in the field, Transporters in Drug Discovery and Development provides a comprehensive and practical guide to drug transporter families that are the most important for drug discovery and development. It covers: an overview of transporter families and organ distribution; clinical relevant drug-drug interaction; clinical relevant polymorphism; drug transporter related pharmacokinetic, pharmacodynamics and toxicity; in vitro/in vivo probes of drug transport studies; the practical methodologies of industrial transporter screening and translational aspect in drug discovery and developments. - A comprehensive overview of drug transporter families and their clinical relevance in drug discovery and development - Balanced coverage of molecular biology aspects and functional outcomes - State of art knowledge related to transporter-mediated DDI and the clinical relevance in pharmacokinetics, dynamics, and toxicity
Download or read book Renal Drug Transporters clinical Significance and Role in Drug drug Interactions written by Jia Yin and published by . This book was released on 2016 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug transporters play an important role in drug disposition and can be major determinants of drug pharmacokinetics, pharmacodynamics and toxicity. In contrast to drug metabolizing enzymes, which mainly concentrate in the liver and small intestine, drug transporters are expressed ubiquitously throughout human body. In human kidney, drug transporters are primarily expressed in the basolateral and apical membranes of proximal tubule cells and often work in tandem to secrete therapeutic drugs and their metabolites into tubular lumen. Furthermore, transporter-mediated drug-drug interactions (DDIs) have become a significant clinical concern as they can adversely impact drug disposition, efficacy, and toxicity. The overall goal of my research project is to understand the clinical significance of renal drug transporters and their role in drug-drug interactions. An analysis of the top 200 prescribed drugs in U.S. and their DDI studies suggests that there is considerable potential for clinically significant renal DDI to occur among commonly used drugs. Potent drug transport inhibitors elicit significant interactions in vivo that approach maximums predicted from in vitro-derived inhibition kinetics. However, high-magnitude renal DDIs in the clinical setting appear to be rare, which may partly be due to a lack of potent in vivo inhibitors, low fraction of net secretion of victim drugs, and compensating transport pathways for the victim drug. Our analysis also identified two widely used antihypertensive drugs, atenolol and hydrochlorothiazide that are cleared predominantly by the kidney but the molecular mechanisms involved in its renal secretion are virtually unknown. Using a panel of HEK cell lines stably expressing major renal drug transporters and absolute quantification of membrane transporter proteins by LC-MS/MS, we found that atenolol is an excellent substrate for the renal organic cation transporter 2 (hOCT2), multidrug and toxin extrusion proteins 1 and 2-K (hMATE1 and 2-K). It can inhibit but not be transported by renal organic anion transporters 1 and 3 (hOAT1 and hOAT3). We also demonstrate unidirectional transepithelial transport of atenolol in an hOCT2/hMATE1 double-transfected MDCK cell culture model. Our data suggest that renal secretion of atenolol is mediated by hOCT2/hMATEs pathway. On the other hand, hydrochlorothiazide was identified to be a substrate of both organic cation transporters hOAT1 and hOAT3 and organic anion transporters hOCT2 and hMATE2-K. However, hOCT2 and hMATE2-K showed much lower affinity and transport efficiency for hydrochlorothiazide than hOAT1 and hOAT3. Combined with findings from other investigators, we propose that renal tubular secretion of hydrochlorothiazide is mediated by two parallel pathways, with hOATs/multidrug resistance-associated protein 4 (hMRP4) being the major one and hOCT2/hMATE2-K being a minor pathway. Our in vitro inhibition studies using potent hOAT1/3 inhibitors also suggest that caution should be taken when hydrochlorothiazide is co-prescribed with potent hOAT1/3 inhibitors, as renal secretion is not only important for its elimination, it may also play a role in its efficacy. Emerging evidence suggests that renal hOCT2 and hMATE1/2-K exhibit substrate-dependent inhibition but the impact on renal drug secretion and intracellular accumulation is unknown. Regulatory agencies recently developed guidelines for transporter-mediated DDI risk assessment but the potential influence of probe substrate choice on prediction is not clear. Using drug substrates, we showed that inhibition of the renal basolateral organic cation transporter 2 by classic clinical inhibitors is highly substrate-dependent, leading to strikingly different DDI predictions. In contrast, inhibition of the apical multidrug and toxin extrusion proteins is less affected by substrate choice. Using a cell culture model simulating tubular secretion, we further demonstrate that substrate-dependent inhibition can shift the major substrate-inhibitor interacting site between apical and basolateral transporters, leading to different effects on intracellular drug accumulation. These findings revealed the complex and dynamic nature of substrate-inhibitor interactions in multispecific drug transporters. In summary, this dissertation research has evaluated the clinical significance of renal DDIs, demonstrated the important role of renal transporters in the clearance and efficacy of two widely used antihypertensive drugs and highlighted the necessity of considering substrate-dependent inhibition in predicting transporter-mediated DDIs
