Enzyme Kinetics in Drug Metabolism (2^nd Ed., 2nd ed. 2021) Fundamentals and Applications Methods in Molecular Biology Series, Vol. 2342

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.

PART I: UNDERLYING PRINCIPLES OF ENZYME KINETICS

1. Fundamentals of Enzyme Kinetics – Michaelis-Menten and Non-Michaelis Type (Atypical) Enzyme Kinetics

Eleanore Seibert and Timothy S. Tracy

2. Reversible Mechanisms of Enzyme Inhibition and Resulting Clinical Significance

Barbara Ring, Steven A. Wrighton, and Michael Mohutsky

3. Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions

Michael Mohutsky and Stephen D. Hall

4. Multi-enzyme Kinetics and Sequential Metabolism

Larry C. Wienkers and Brooke Rock

Nigel J Waters, R Scott Obach, and Li Di

6. Numerical Methods for Modeling Enzyme Kinetics

Jaydeep Yadav, Ken Korzekwa, and Swati Nagar

Part II: Crystal Structure, Biochemistry, and Impact On Enzyme Kinetics

7. Crystal Structures of Drug-Metabolizing CYPs

D. Fernando Estrada, Amit Kumar, Christopher S. Campomizzi, and Natalie Jay

8. The Structure and Mechanism of Drug Transporters

Arthur G. Roberts

PART III: KINETICS OF DRUG METABOLIZING ENZYMES AND TRANSPORTERS

9. Enzyme Kinetics of Oxidative Metabolism – Cytochromes P450

Ken Korzekwa

10. Enzyme Kinetics, Pharmacokinetics, and Inhibition of Aldehyde oxidase

Erickson M. Paragas, Kanika Choughule, Jeffrey P. Jones, and John T. Barr

11. Enzyme Kinetics of PAPS-sulfotransferase

Margaret O. James

12. Enzyme Kinetics of Uridine Diphosphate Glucuronosyltransferases (UGTs)

Jin Zhou, Upendra Argikar, and John O. Miners

13. Principles and Experimental Considerations for In Vitro Transporter Interaction Assays

Sid Bhoopathy, Chris Bode, Vatsala Naageshwaran, Erica Weiskircher-Hildebrandt,

Venkata Mukkavilli, and Ismael J. Hidal

PART IV: MODELING CONSIDERATIONS

14. Prediction of Drug Clearance from Enzyme and Transporter Kinetics

Priyanka R. Kulkarni, Amir S. Youssef, and Aneesh A. Argikar

15. Systems Biology Approaches to Enzyme Kinetics

Nnenna A. Finn, Andrew D. Raddatz, and Melissa L. Kemp

PART V: APPLICATION TO THE CLINIC AND REGULATORY CONSIDERATIONS

16. Variability in Human In Vitro Enzyme Kinetics

Christopher R. Gibson, Ying-Hong Wang, Ninad Varkhede, and Bennett Ma

17.Sources of Interindividual Variability

Yvonne S. Lin,Kenneth E. Thummel,  Brice D. Thompson,  Rheem A. Totah, and Christi W. Cho

Aarzoo Thakur, Md Masud Parvez, J. Steven Leeder, and Bhagwat Prasad

Xinning Yang, Jianghong Fan, and Lei Zhang

PART VI: CASE STUDIES 

20. Case Study 1: Practical Considerations with Experimental Design and Interpretation

John T Barrand Otito Iwuchukwu

21. Case Study # 2: Practical Analytical Considerations for Conducting In Vitro Enzyme Kinetic Studies

Upendra A. Argikar and Swati Nagar

22. Case Study 3: Criticality of High-Quality Curve Fitting: Getting a K_m,app isn’t as Simple as it May Seem

David M. Stresser and Arian Emami-Riedmaier

23. Case Study 4 Application of Basic Enzyme Kinetics To Metabolism Studies  – Real Life Examples

Yongmei Li, Michelle McCabe, Lalitha Podila, Timothy S. Tracy, and Donald Tweedie

24. Case Study 5. Predicting the Drug Interaction Potential for Inhibition of CYP2C8 by Montelukast

Ken Korzekwa

25 Case Study 6: Deconvoluting Hyperbilirubinemia: Differentiating between Hepatotoxicity and Reversible Inhibition of UGT1A1, MRP2 or OATP1B1 in Drug Development

Ian Templeton, Gary Eichenbaum, Rucha Sane, Jin Zhou

26. Case Study 7. Transporters Case Studies: In Vitro Solutions for Translatable Outcomes­

Sid Bhoopathy, Chris Bode, Vatsala Naageshwaran, Erica Weiskircher-Hildebrandt, Venkata Mukkavilli, and Ismael J. Hidalgo

^27. Case Study 8: Status of the Structural Mass Action Kinetic Model of P-gp Mediated Transport through Confluent Cell Monolayers

Joe Bentz and Harma Ellens

28. Case Study 9: Probe-Dependent Binding Explains Lack of CYP2C9 Inactivation by 1-Aminobenzotriazole (ABT)

Jasleen K. Sodhi and Jason S. Halladay

29. Case Study 10: A Case to Investigate Acetyl Transferase Kinetics

Jennifer L Dumouchel and Valerie M Kramlinger

30. Case Study 11.  Considerations for Enzyme Mapping Experiments: Interaction between the Aldehyde Oxidase Inhibitor Hydralazine and Glutathione

 Rachel D. Crouch, Jessica L. Beers, and Klarissa D. Jackson2

31. Case Study 12: Roadmap to Quantifying Ago2-Mediated siRNA Metabolic Activation Kinetics

Includes cutting-edge methods and protocols

Provides step-by-step detail essential for reproducible results

Contains key notes and implementation advice from the experts