Enzyme Kinetics in Drug Metabolism: Fundamentals and Applications

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 Barr and 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