Enzyme Kinetics in Drug Metabolism

Enzyme Kinetics in Drug Metabolism（Methods in Molecular Biology）

药物代谢的酶动力学：基础知识与应用第2版
生物化学

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作者

Swati Nagar Upendra A. Argikar Donald Tweedie

出版社

Humana Press

出版时间

2022年07月17日

装帧

平装

ＩＳＢＮ

9781071615560

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页码

912

开本

10.00 x 7.00 x 1.80

语种

英文

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This second edition further develops the principles of applying kinetic principles to drug metabolizing enzymes and transporters. Chapters are divided into six sections detailing fundamental principles of enzyme kinetics, enzyme and transporter structures, highlighting specific oxidative and conjugative drug metabolizing enzymes and drug transporters, modeling approaches for drug metabolizing enzymes and transporters, understanding of variability both experimental and interindividual (pharmacogenomic), and expanded case studies that provide real life examples of applying these principles. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, in some cases step-by-step instructions with readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls with extensive cross referencing to assist in learning. Authoritative and fully updated, Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications, Second Edition serves as a practical teaching tool for novice and advanced scientists interested in the fundamental concepts.

Fundamentals of Enzyme Kinetics – Michaelis-Menten and Non-Michaelis Type (Atypical) Enzyme Kinetics.- Reversible Mechanisms of Enzyme Inhibition and Resulting Clinical Significance.- Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions.- Multi-enzyme Kinetics and Sequential Metabolism.- Consideration of the Unbound Drug Concentration in Enzyme Kinetics.- Numerical Methods for Modeling Enzyme Kinetics.- Crystal Structures of Drug-Metabolizing CYPs.- The Structure and Mechanism of Drug Transporters.- Enzyme Kinetics of Oxidative Metabolism – Cytochromes P450.- Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde oxidase.- Enzyme Kinetics of PAPS-sulfotransferase.- Enzyme Kinetics of Uridine Diphosphate Glucuronosyltransferases (UGTs).- Principles and Experimental Considerations for In Vitro Transporter Interaction Assays.- Prediction of Drug Clearance from Enzyme and Transporter Kinetics.- Systems Biology Approaches to Enzyme Kinetics.- Variability in Human In Vitro Enzyme Kinetics.- Sources of Interindividual Variability.- Ontogeny of Drug Metabolizing Enzymes.- How Science is Driving Regulatory Guidances.- Case Study 1: Practical Considerations with Experimental Design and Interpretation.- Case Study # 2: Practical Analytical Considerations for Conducting In Vitro Enzyme Kinetic Studies.- Case Study 3: Criticality of High-Quality Curve Fitting: Getting a Km,app isn’t as Simple as it May Seem.- Case Study 4 Application of Basic Enzyme Kinetics To Metabolism Studies – Real Life Examples.- Case Study 5. Predicting the Drug Interaction Potential for Inhibition of CYP2C8 by Montelukast.- Case Study 6: Deconvoluting Hyperbilirubinemia: Differentiating between Hepatotoxicity and Reversible Inhibition of UGT1A1, MRP2 or OATP1B1 in Drug Development.- Case Study 7. Transporters Case Studies: In Vitro Solutions for Translatable Outcomes.- Case Study 8: Status of the Structural Mass Action Kinetic Model of P-gp Mediated Transport through Confluent Cell Monolayers.- Case Study 9: Probe-Dependent Binding Explains Lack of CYP2C9 Inactivation by 1-Aminobenzotriazole (ABT).- Case Study 10: A Case to Investigate Acetyl Transferase Kinetics.- Case Study 11. Considerations for Enzyme Mapping Experiments: Interaction between the Aldehyde Oxidase Inhibitor Hydralazine and Glutathione.- Case Study 12: Roadmap to Quantifying Ago2-Mediated siRNA Metabolic Activation Kinetics.

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