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The The Biochemistry of Drug Metabolism, v. 1 - The Biochemistry of Drug Metabolism Principles, Redox Reactions, Hydrolyses... The The Biochemistry of Drug Metabolism, v. 1 - The Biochemistry of Drug Metabolism Principles, Redox Reactions, Hydrolyses (Paperback)
Bernard Testa, Stefanie D. Kramer
R1,825 R1,519 Discovery Miles 15 190 Save R306 (17%) Shipped within 7 - 12 working days

The first of the two volumes is divided into three parts. Part One begins by introducing xenobiotics in the broad context of physiological metabolism, and continues with an overview of the processes of drug disposition and metabolism. It then goes on to summarize the macroscopic and microscopic locations of drug metabolism in animals and humans. This is followed by an introduction to the all-important issue of the consequences of drug and xenobiotic metabolism, providing an initial overview of pharmacokinetic, pharmacological and toxicological consequences. The last chapter examines drug metabolism in the context of drug research, with a focus on medicinal chemistry.
The second part is a major component of the book, corresponding to the role of oxidoreductases as major agents of metabolism. Cytochromes P450 receive particular attention, namely their multiplicity, structure, catalytic mechanisms, and the various reactions they catalyze, while other oxidoreductases are also presented, such as flavin monooxygenases, monoamine oxidases and other amine oxidases, aldehyde oxidase and xanthine dehydrogenase, peroxidases, and dehydrogenases-reductases. Each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials.
Part Three begins with a survey of the classification, properties and catalytic mechanism of the innumerable hydrolases known or suspected to play a role in xenobiotic metabolism. The focus then shifts to a systematic presentation of the various substrate classes, namely carboxylic esters, amides and peptides, lactams and lactones, esters of inorganic acids, alkene and arene epoxides, and some miscellaneous hydrolyzable moieties.
With a foreword by Prof Leslie Z. Benet, the world's best and best-known biopharmaceutical scientist

The The Biochemistry of Drug Metabolism, v. 2 - The Biochemistry of Drug Metabolism Conjugations, Consequences of Metabolism,... The The Biochemistry of Drug Metabolism, v. 2 - The Biochemistry of Drug Metabolism Conjugations, Consequences of Metabolism, Influencing Factors (Paperback)
Bernard Testa, Stefanie D. Kramer
R1,290 R1,172 Discovery Miles 11 720 Save R118 (9%) Shipped within 7 - 12 working days

Volume Two contains the last four parts of this work. Part 4 is devoted to the huge field of conjugation reactions, with much information being given on transferases. As in the two preceding parts, each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials. The reactions examined here include methylation, sulfation, glucuronidation, acetylation, conjugation with glutathione, while there is also a rigorous presentation of the pivotal role of xenobiotic-coenzyme A conjugates as a crossroads to various metabolic reactions.
The next part examines the consequences of drug and xenobiotic metabolism in a pharmacological and toxicological perspective, with due attention paid to full activation, as is found with prodrugs, and to the worrying case of xenobiotic toxification.
Parts 6 and 7 cover the inter-individual and intra-individual factors that influence drug metabolism, starting with an introduction to evolutionary events leading to species differences in the metabolism of xenobiotics and to polymorphisms within a particular species. Focusing on humans, the most relevant polymorphic drug-metabolizing enzymes are discussed, concentrating on ethnic differences and on the consequences for the pharmacokinetic behavior of affected drugs, while also introducing sex-dependent metabolic reactions.
The final part introduces the mechanisms leading to increases or decreases in enzyme activities as the concept of enzyme induction via nuclear receptors and the different mechanisms of enzyme inhibition are explained. With these basics in mind, various influencing factors are discussed, including physiological and pathological conditions, as well as drugs, nutrients and environmental agents with a special focus on drug-drug interactions.
With a foreword by Prof Leslie Z. Benet -- the best and best-known biopharmaceutical scientist worldwide.

Pharmacokinetic Profiling in Drug Research - Biological, Physicochemical, and Computational Strategies (Hardcover): Bernard... Pharmacokinetic Profiling in Drug Research - Biological, Physicochemical, and Computational Strategies (Hardcover)
Bernard Testa, Stefanie D. Kramer, Heidi Wunderli-Allenspach, Gerd Folkers
R4,451 R3,956 Discovery Miles 39 560 Save R495 (11%) Shipped within 7 - 12 working days

Informatics and robotics are the workhorses of a technological revolution in drug research. On them are based combinatorial chemistry, which yields compounds by the many thousands, and high-throughput bioassays, which screen them for activity. The results are avalanches of 'hits', which invade the databases like swarms of locusts. But far from being a plague, these innumerable compounds become a blessing if properly screened for 'drugability', i.e., for 'drug-like' properties such as good pharmacokinetic (PK) behavior. Pharmacokinetic profiling of bioactive compounds has, thus, become a sine qua non condition for cherry-picking the most promising hits. Just as important, but less visible, are the structure-property and structure-ADME relations, which emerge from PK profiling and provide useful feedback when designing new synthetic series. As a result, the screening, design, and optimization of pharmacokinetic properties has become the bottleneck and a major challenge in drug research. To shorten the time-consuming development and high rate of attrition of active compounds ultimately doomed by hidden pharmacokinetic defects, powerful biological, physicochemical, and computational approaches are being developed, whose objectives are to increase the clinical relevance of drug design and to eliminate as soon as possible compounds with unfavorable physicochemical properties and pharmacokinetic profiles.
The profiling of ADME properties (absorption, distribution, metabolism, and excretion) is the topic of this book. Following the extraordinary success of the previous work ('Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical, and Computational Strategies', Eds. B. Testa, H. van de Waterbeemd, G. Volkers, R. Guy, Verlag Helvetica Chimica Acta, Zurich, 2001, 655 pages), there was a need for an essentially new edition focusing on the latest theoretical and technological breakthroughs. In this unique work, international authorities and practicing experts from academia and industry offer state-of-the-art presentations of concepts, methods and technologies now in use or development in drug research. The biological strategies emphasized in the book include cell cultures, drug-metabolizing enzymes, transporters and plasma protein binding. The physicochemical strategies focus on artificial membrane-permeability assays, on solubility and lipophilicity and related molecular properties as factors and predictors of pharmacokinetic behavior, and on stability and solid-state properties. Computational strategies comprize the exploration of property spaces, pharmacophore searching to predict biotransformation and enzyme inhibition, and expert systems to process biopharmaceutical profiling data.
In addition to its 28 chapters, the book includes a CD-ROM containing the invited lectures, oral communications, and posters (in full version) presented at the Third LogP Symposium, 'Physicochemical and Biological Profiling in Drug Research', held at the Federal Institute of Technology (ETH) of Zurich in March 2004.

The Biochemistry of Drug Metabolism - Principles, Redox Reactions, Hydrolyses, Two Volume Set (Paperback): Bernard Testa,... The Biochemistry of Drug Metabolism - Principles, Redox Reactions, Hydrolyses, Two Volume Set (Paperback)
Bernard Testa, Stefanie D. Kramer
R2,707 R1,928 Discovery Miles 19 280 Save R779 (29%) Shipped within 7 - 13 working days

Offering a conceptual and factual presentation of the metabolism of drugs and other xenobiotics, these two volumes distinctly focus on the biochemistry, with an emphasis on xenobiotic-metabolizing enzymes, their reactions and regulations.
The first volume is divided into three parts. Part One begins by introducing xenobiotics in the broad context of physiological metabolism, and continues with an overview of the processes of drug disposition and metabolism. It then goes on to summarize the macroscopic and microscopic locations of drug metabolism in animals and humans. This is followed by an introduction to the all-important issue of the consequences of drug and xenobiotic metabolism, providing an initial overview of pharmacokinetic, pharmacological and toxicological consequences. The last chapter examines drug metabolism in the context of drug research, with a focus on medicinal chemistry.
The second part is a major component of the book, corresponding to the role of oxidoreductases as major agents of metabolism. Cytochromes P450 receive particular attention, namely their multiplicity, structure, catalytic mechanisms, and the various reactions they catalyze, while other oxidoreductases are also presented, such as flavin monooxygenases, monoamine oxidases and other amine oxidases, aldehyde oxidase and xanthine dehydrogenase, peroxidases, and dehydrogenases-reductases. Each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials.
Part Three begins with a survey of the classification, properties and catalytic mechanism of the innumerable hydrolases known or suspected to play a role in xenobiotic metabolism. The focus then shifts to a systematic presentation of the various substrates classes, namely carboxylic esters, amides and peptides, lactams and lactones, esters of inorganic acids, alkene and arene epoxides, and some miscellaneous hydrolyzable moieties.
Volume Two contains the last four parts of this work. Part 4 is devoted to the huge field of conjugation reactions, with much information being given on transferases. As in the two preceding parts, each drug-metabolizing enzyme or enzyme family begins with an Enzyme Identity Card summarizing its nomenclature and biochemical essentials. The reactions examined here include methylation, sulfation, glucuronidation, acetylation, conjugation with glutathione, while there is also a rigorous presentation of the pivotal role of xenobiotic-coenzyme A conjugates as a crossroads to various metabolic reactions.
The next part examines the consequences of drug and xenobiotic metabolism in a pharmacological and toxicological perspective, with due attention paid to full activation, as is found with prodrugs, and to the worrying case of xenobiotic toxification.
Parts 6 and 7 cover the inter-individual and intra-individual factors that influence drug metabolism, starting with an introduction to evolutionary events leading to species differences in the metabolism of xenobiotics and to polymorphisms within a particular species. Focusing on humans, the most relevant polymorphic drug-metabolizing enzymes are discussed, concentrating on ethnic differences and on the consequences for the pharmacokinetic behavior of affected drugs, while also introducing sex-dependent metabolic reactions.
The final part introduces the mechanisms leading to increases or decreases in enzyme activities as the concept of enzyme induction via nuclear receptors and the different mechanisms of enzyme inhibition are explained. With these basics in mind, various influencing factors are discussed, including physiological and pathological conditions, as well as drugs, nutrients and environmental agents with a special focus on drug-drug interactions.
With a foreword by Prof Leslie Z. Benet, the renowned biopharmaceutical scientist.

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