05373nam 2200673Ia 450 991014398210332120230721030237.01-282-02206-797866120220670-470-18792-10-470-18791-3(CKB)1000000000376120(EBL)427662(OCoLC)476269799(SSID)ssj0000141607(PQKBManifestationID)11148635(PQKBTitleCode)TC0000141607(PQKBWorkID)10090175(PQKB)10099530(MiAaPQ)EBC427662(Au-PeEL)EBL427662(CaPaEBR)ebr10296311(CaONFJC)MIL202206(EXLCZ)99100000000037612020070415d2008 uy 0engur|n|---|||||txtccrDrug-drug interactions in pharmaceutical development[electronic resource] /edited by Albert P. LiHoboken, N.J. Wiley-intersciencec20081 online resource (261 p.)Wiley series in drug discovery and developmentDescription based upon print version of record.0-471-79441-4 Includes bibliographical references and index.DRUG-DRUG INTERACTIONS IN PHARMACEUTICAL DEVELOPMENT; CONTENTS; Preface; Contributors; 1 In Vitro Evaluation of Metabolic Drug-Drug Interactions: Concepts and Practice; 1.1 Introduction; 1.2 Mechanisms of Adverse Drug-Drug 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 Cytosol1.6 Mechanisms of Metabolic Drug-Drug Interactions; 1.7 Mechanism-Based Approach for Evaluation of Drug-Drug 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 Drug-Drug Interaction Potential; 1.8.1 Study 1: Metabolic Phenotyping 1-Metabolite Identification; 1.8.2 Study 2: Metabolic Phenotyping 2-Identification of Major Metabolic Pathways1.8.3 Study 3: Metabolic Phenotyping 3-Identification of P450 Isoform Pathways (P450 Phenotyping)1.8.4 Study 4: CYP Inhibitory Potential; 1.8.5 Study 5: Enzyme Induction Potential; 1.8.6 Study 6: In Vitro Empirical Drug-Drug Interactions; 1.9 Data Interpretation; 1.9.1 Pathway Evaluation; 1.9.2 P450 Inhibition; 1.9.3 P450 Induction; 1.10 Conclusion; References; 2 In Vitro Approaches to Anticipating Clinical Drug Interactions; 2.1 In Vitro Systems for Human CYP450 Metabolism; 2.1.1 Incubation Buffer (pH and Ionic Strength); 2.1.2 MgCl(2) and Cytochrome b(5); 2.1.3 Nonspecific Binding2.1.4 Organic Solvents and Excipients2.2 Analysis of Data from In Vitro Systems; 2.2.1 Linear Transformation of Michaelis-Menten Equation (Lineweaver-Burk and Eadie-Hofstee); 2.2.2 Nonlinear Regression Analysis of Hyperbolic Kinetic Data; 2.2.3 Consideration of Non-Michaelis-Menten Kinetics; 2.3 Use of In Vitro Kinetic Data to Predict In Vivo Clearance; 2.3.1 Calculation of In Vitro (Predicted) Hepatic Clearance; 2.3.2 Comparison of In Vitro (Predicted) with In Vivo Hepatic Clearance; 2.4 Use of In Vitro Kinetic Data to Predict Drug-Drug Interactions2.4.1 Choice of Probe Substrates for Inhibition Studies2.4.2 Determining the Mechanism of CYP450 Inhibition; 2.4.3 Prediction of In Vivo Drug-Drug Inhibition Interactions from In Vitro Data; 2.5 Consideration of Non-CYP Enzymatic Systems; 2.5.1 Flavin-Containing Monooxygenase (FMO); 2.5.2 UDP-glucuronosyltransferase (UGT); 2.5.3 Sulfotransferase (SULT); 2.5.4 N-Acetyltransferase (NAT); 2.5.5 Methyltransferase; 2.5.6 Epoxidase Hydrolase; 2.5.7 Aldehyde Oxidase and Dehydrogenase; 2.5.8 Glutathione-S-transferase (GST); 2.6 Summary; 2.7 Acknowledgments; References3 Inhibition of Drug-Metabolizing Enzymes and Drug-Drug Interactions in Drug Discovery and DevelopmentDrug-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.Wiley series in drug discovery and development.Drug interactionsDrug developmentDrug interactions.Drug development.615.7045615/.7045Li A. P946693MiAaPQMiAaPQMiAaPQBOOK9910143982103321Drug-drug interactions in pharmaceutical development2138899UNINA