Integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development Book

	Introduction
Sect. I	Introduction
1	Rationale for the Effective Use of Pharmacokinetics and Pharmacodynamics in Early Drug Development	1
2	The Case for Preclinical Pharmacodynamics	7
3	Utility of Kinetic, Dynamic, and Metabolic Data in Nonclinical Pharmacology/Toxicology Studies	15
Sect. II	Preclinical Pharmacokinetic & Pharmacodynamic Studies
4	Pharmacokinetics and Drug Metabolism in Animal Studies (ADME, Protein Binding, Mass Balance, Animal Models)	23
5	Nonclinical Considerations: Disposition of Drugs	33
6	Use of Acute Toxicity Data in the Design and Interpretation of Subchronic and Chronic Toxicity Studies	39
7	Use of Pharmacokinetics and Pharmacodynamics in Preclinical Studies to Guide Dosage Escalation Schemes in Phase I Studies of Anticancer Drugs	49
8	Use of Toxicokinetic Principles in Drug Development: Bridging Preclinical and Clinical Studies	55
Sect. III	Methodology for Preclinical Pharmacodynamic Studies
9	Preclinical Pharmacodynamics of Central Nervous System Active Agents	69
10	Preclinical Pharmacodynamics of Antihypertensives	81
11	Preclinical Pharmacodynamics of Anxiolytics: Effects of Chronic Benzodiazepine Administration	91
12	Guidelines for Development of a New Diuretic Agent	97
13	Preclinical Pharmacodynamics of Anti-Inflammatory Drugs	105
Sect. IV	Preclinical & Clinical Pharmacokinetics
14	The Role of Pharmacokinetics in the Drug Development Process	115
15	Implementation of an Effective Pharmacokinetics Research Program in Industry	125
16	Pharmacoepidemiology, Population Pharmacokinetics and New Drug Development	137
17	Assessment of Pharmacokinetic Drug Interactions in Clinical Drug Development	149
Sect. V	Clinical Pharmacodynamics
18	Pharmacokinetic/Pharmacodynamic Models and Methods	159
19	Pharmacokinetic and Pharmacodynamic Modeling Applied to Anesthetic Drugs	179
20	Pharmacodynamic/Pharmacokinetic Relationships for Rapidly Acting Drugs (NSAIDS) in Rheumatoid Arthritis: Problems and Preliminary Solutions	193
21	The Value of Plasma-Warfarin Measurement	201
22	Clinical Pharmacodynamics of Cardiovascular Agents: Focus on Sudden Cardiac Death	207
23	The Benzodiazepines: Kinetic-Dynamic Relationships	217
Sect. VI	Application of Pharmacodynamics & Pharmacokinetics in the Drug Development Process
24	The Integration of Pharmacodynamics and Pharmacokinetics in Rational Drug Development	225
25	Concentration-Controlled Trials: Basic Concepts, Design, and Implementation	239
Sect. VII	Summary Report
26	Opportunities for Integration of Pharmacokinetics, Pharmacodynamics and Toxicokinetics in Rational Drug Development	249
	Author Index	265
	Subject Index	267