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This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.
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
This book illustrates, in a comprehensive manner, the most crucial principles involved in pharmacology and allied sciences. The title begins by discussing the historical aspects of drug discovery, with up to date knowledge on Nobel Laureates in pharmacology and their significant discoveries. It then examines the general pharmacological principles - pharmacokinetics and pharmacodynamics, with in-depth information on drug transporters and interactions. In the remaining chapters, the book covers a definitive collection of topics containing essential information on the basic principles of pharmacology and how they are employed for the treatment of diseases. Readers will learn about special topics in pharmacology that are hard to find elsewhere, including issues related to environmental toxicology and the latest information on drug poisoning and treatment, analytical toxicology, toxicovigilance, and the use of molecular biology techniques in pharmacology. The book offers a valuable resource for researchers in the fields of pharmacology and toxicology, as well as students pursuing a degree in or with an interest in pharmacology.
The peroral application (swallowing) of a medicine means that the body must first resorb the active substance before it can begin to take effect. The efficacy of drug uptake depends on the one hand on the chemical characteristics of the active substance, above all on its solubility and membrane permeability. On the other hand, it is determined by the organism's ability to absorb pharmaceuticals by way of specific transport proteins or to excrete them. Since many pharmacologically active substances are poorly suited for oral intake, a decisive criterion for the efficacy of a medicine is its so-called bioavailability. Written by an international team from academia and the pharmaceutical industry, this book covers all aspects of the oral bioavailability of medicines. The focus is placed on methods for determining the parameters relevant to bioavailability. These range from modern physicochemical techniques via biological studies in vitro and in vivo right up to computer-aided predictions. The authors specifically address possibilities for optimizing bioavailability during the early screening stage for the active substance. Its clear structure and comprehensive coverage make this book equally suitable for researchers and lecturers in industry and teaching.
Since publication of the Second Edition in 1989, numerous innovations have occurred that affect the way scientists look at issues in the field of percutaneous absorption. Focusing on recent advances as well as updating and expanding the scope of topics covered in the previous edition, Percutaneous Absorption, Third Edition provides thorough coverage of the skin's role as an important portal of entry for chemicals into the body. Assembles the work of nearly 80 experts-30 more than the Second Edition-into a unified, comprehensive volume that contains the latest ideas and research! Complete with nearly 600 drawings, photographs, equations, and tables and more than 1600 bibliographic citations of pertinent literature, Percutaneous Absorption, Third Edition details the applied biology of percutaneous penetration factors that affect skin permeation, such as age, vehicles, metabolism, hydration of skin, and chemical structure in vivo and in vitro techniques for measuring absorption, examining factors influencing methodology such as animal models, volatility of test compound, multiple dosage, and artificial membranes procedures for use in transdermal delivery, exploring topics such as effects of penetration enhancers on absorption, optimizing absorption, and the topical delivery of drugs to muscle tissue And presents new chapters on mathematical models cutaneous metabolism prediction of percutaneous absorption in vitro absorption methodology dermal decontamination concentration of chemicals in skin transdermal drug delivery mechanisms of absorption safety evaluation of cosmetics absorption of drugs and cosmetic ingredients nail penetration Emphasizes human applications-particularly useful for pharmacists, pharmacologists, dermatologists, cosmetic scientists, biochemists, toxicologists, public health officials, manufacturers of cosmetic and toiletry products, and graduate students in these disciplines! An invaluable reference source for readers who need to keep up with the latest developments in the field, Percutaneous Absorption, Third Edition is also an excellent experimental guide for laboratory personnel.
This Book serves to highlight the mechanisms related to the low intestinal drug absorption, the strategies to overcome the obstacles or intestinal drug absorption, and in situ, in vitro, and in silico methodologies to predict to intestinal drug absorption. This Book presents a series of drug absorption studies and related technologies that predict intestinal permeation of drugs that govern the pharmacokinetic features of therapeutic drugs. It also contains the mechanistic understanding regarding the first-pass metabolism and intestinal efflux that modulate the pharmacokinetics of drug and suggest the formulation strategies to enhance the bioavailability of investigated drugs.
The highly experienced authors here present readers with step-wise, detail-conscious information to develop quality pharmaceuticals. The book is made up of carefully crafted sections introducing key concepts and advances in the areas of dissolution, BA/BE, BCS, IVIC, and product quality. It provides a specific focus on the integration of regulatory considerations and includes case histories highlighting the biopharmaceutics strategies adopted in development of successful drugs.
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint
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.
This volume of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) will show that pharma cology has finally arrived as a true discipline in its own right, and is no longer the handmaiden of organic chemistry and physiology. Instead it is an amalgam of all the biological sciences including biochemistry, biophysical chemistry, physiology, pathology and clinical medicine. In the volumes that make up Concepts in Bioche mical Pharmacology we hope to convince Medical Schools what should now be obvious, that pharmacology is no longer that dull topic bridging the basic sciences with medicine, but is probably the most important subject in the medical curriculum. We are grateful for the advice of Dr. BYRON CLARKE, Director of the Pharmacology-Toxicology Program at the National Insti tutes of Health, whose support made possible much of the work described in this volume. Contents Section One: Routes of Drug Administration Chapter 1: Biological Membranes and Their Passage by Drugs. C. A. M. HOGBEN 1 References. . . . . . . . . . . . . . . . . . . . . . . . . . 8 Chapter 2: Absorption of Drugs from the Gastrointestinal Tract. L. S. SCHANKER. With 5 Figures. 9 I. Introduction. . . . . . . . . . . . . . . . . . . . . . . 9 II. Methods of Study. . . . . . . . . . . . . . . . . . . . . 9 III. Absorption from the Stomach . . . . . . . . . . . . . . . 11 IV. Intestinal Absorption of Non-Electrolytes and Weak Electrolytes 15 V. Absorption of Weak Electrolytes from the Colon and Rectum 18 VI. Intestinal Absorption of Organic Ions. . . . . . . . . . 19 VII. Intestinal Absorption of Macromolecules . . . . . . . . . . 19 VIII. Active Transport across the Intestinal Epithelium . . . . . 20 IX. Effect of EDTA on Drug Absorption from the Intestine . . . . . . .