Description
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. 1. Enzyme Kinetics in Drug Metabolism – Fundamentals and Applications Swati Nagar, Upendra A. Argikar, and Donald J. Tweedie Part I. Fundamentals of Enzyme Kinetics 2. Fundaments of Enzyme Kinetics Eleanore Seibert and Timothy S. Tracy 3. Different Enzyme Kinetic Models Eleanore Seibert and Timothy S. Tracy 4. Reversible Mechanisms of Enzyme Inhibitors and Resulting Clinical Significance Barbara Ring, Steven A. Wrighton, and Michael Mohutsky 5. Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions Michael Mohutsky and Stephen D. Hall 6. Multi-Enzyme Kinetics and Sequential Metabolism Larry C. Wienkers and Brooke VandenBrink 7. Consideration of the Unbound Drug Concentration in Enzyme Kinetics Nigel J. Waters, R. Scott Obach, and Li Di Part II. Kinetics of Drug Metabolizing Enzymes and Transporters 8. Enzyme Kinetics of Oxidative Metabolism – Cytochromes P450 Ken Korzekwa 9. Enzyme Kinetics, Pharmacokinetics, Inhibition, and Regioselectivity of Aldehyde Oxidase John T. Barr, Kanika Choughule, and Jeffrey P. Jones 10. Enzyme Kinetics of Conjugative Enzymes – PAPS Margaret O. James 11. Enzyme Kinetics of Uridine Diphosphate Glucuronosyltransferases (UGTs) Jin Zhou and John Miners 12. Principles and Experimental Considerations for in vitro Transporter Interaction Assays Sid Bhoopathy, Chris Bode, Vatsala Naageshwaran, Erica A. Wiskercher, and Ismael J. Hidalgo Part III. Modeling Considerations 13. Rationalising Under-Prediction of Drug Clearance from Enzyme and Transporter Kinetic Data – from in vitro Tools to Mechanistic Modeling Aleksandra Galetin 14. The Structural Model for the Mass Action Kinetic Analysis of P-gp Mediated Transport Through Confluent Cell Monolayers Joseph Bentz and Harma Ellens 15. Systems Biology Approaches to Enzyme Kinetics: Analyzing Network Models of Drug Metabolism Nnena A. Finn and Melissa L. Kemp Part IV. Variability in Kinetics 16. Variability in Human in vitro Enzyme Kinetics Ying-Hong Wang and Christopher R. Gibson 17. Sources of Interindividual Variability Yvonne Lin and Kenneth E. Thummel Part V. Case Studies 18. Case Study 1. Practical Considerations with Experimental Design and Interpretation John T. Barr, Darcy R. Flora, and Otito Iwuchukwu 19. Case Study 2. Practical Analytical Considerations for Conducting in vitro Enzyme Kinetic Studies Upendra A. Argikar and Swati Nagar 20. Case Study 3. Application of Basic Enzyme Kinetics to Metabolism Studies – Real Life Examples Yongmei Li, Michelle McCabe, Lalitha Podila, Timothy S. Tracy, and Donald J. Tweedie 21. Case Study 4. Predicting the Drug Interaction Potential for Inhibition of CYP2C8 by Montelukast Ken Korzekwa 22. Case Study 5. Deconvoluting Hyperbilirubinemia: Differentiating Between Hepatotoxicity and Reversible Inhibition of UGT1A, MRP2 or OATP1B1 in Drug Development Ian Templeton, Gary Eichenbaum, Rucha Sane, and Jin Zhou 23. Case Study 6. Drug Transporters: in vitro Solutions for Translatable Outcomes Sid Bhoopathy, Chris Bode, Vatsala Naageshwaran, Erica A. Weiskircher, and Ismael J. Hidalgo 24. Case Study 7. Compiled Aha Moments in Enzyme Kinetics: Authors’ Experiences Donald J. Tweedie
