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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
5. Consideration of the Unbound Drug Concentration in Enzyme Kinetics
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
18. Ontogeny of Drug Metabolizing Enzymes
Aarzoo Thakur, Md Masud Parvez, J. Steven Leeder, and Bhagwat Prasad
19. How Science is Driving Regulatory Guidances
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 Km, 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
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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
5. Consideration of the Unbound Drug Concentration in Enzyme Kinetics
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
18. Ontogeny of Drug Metabolizing Enzymes
Aarzoo Thakur, Md Masud Parvez, J. Steven Leeder, and Bhagwat Prasad
19. How Science is Driving Regulatory Guidances
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 Km, 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
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