Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications

ISBN-13: 9781627037570 / Angielski / Twarda / 2014 / 538 str.

Swati Nagar; Upendra A. Argikar; Donald J. Tweedie

Opis

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.

Spis treści

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