Drug-Drug Interactions in Pharmaceutical Development [Hardcover]

Drug-Drug Interactions in Pharmaceutical Development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage.Preface.

Contributors.

1 In Vitro Evaluation of Metabolic DrugDrug Interactions: Concepts and Practice (Albert P. Li).

1.1 Introduction.

1.2 Mechanisms of Adverse DrugDrug Interactions.

1.2.1 Pharmacological Interactions.

1.2.2 Pharmacokinetic Interactions.

1.3 Drug Metabolism.

1.3.1 Phase I Oxidation.

1.3.2 Phase II Conjugation.

1.4 CYP Isoforms.

1.5 Human In Vitro Experimental Systems for Drug Metabolism.

1.5.1 Hepatocytes.

1.5.2 Liver Postmitochondrial Supernatant (PMS).

1.5.3 Human Liver Microsomes.

1.5.4 Recombinant P450 Isoforms (rCYP).

1.5.5 Cytosol.

1.6 Mechanisms of Metabolic DrugDrug Interactions.

1.7 Mechanism-Based Approach for Evaluation of DrugDrug Interaction Potential.

1.7.1 Metabolic Phenotyping.

1.7.2 Evaluation of Inhibitory Potential for Drug-Metabolizing Enzymes.

1.7.3 Induction Potential for Drug-Metabolizing Enzymes.

1.8 Experimental Approaches for In Vitro Evaluation of DrugDrug Interaction Potential.

1.8.1 Study 1: Metabolic Phenotyping 1Metabolite Idel-