LEADER 05373nam 2200673Ia 450 001 9910143982103321 005 20230721030237.0 010 $a1-282-02206-7 010 $a9786612022067 010 $a0-470-18792-1 010 $a0-470-18791-3 035 $a(CKB)1000000000376120 035 $a(EBL)427662 035 $a(OCoLC)476269799 035 $a(SSID)ssj0000141607 035 $a(PQKBManifestationID)11148635 035 $a(PQKBTitleCode)TC0000141607 035 $a(PQKBWorkID)10090175 035 $a(PQKB)10099530 035 $a(MiAaPQ)EBC427662 035 $a(Au-PeEL)EBL427662 035 $a(CaPaEBR)ebr10296311 035 $a(CaONFJC)MIL202206 035 $a(EXLCZ)991000000000376120 100 $a20070415d2008 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aDrug-drug interactions in pharmaceutical development$b[electronic resource] /$fedited by Albert P. Li 210 $aHoboken, N.J. $cWiley-interscience$dc2008 215 $a1 online resource (261 p.) 225 1 $aWiley series in drug discovery and development 300 $aDescription based upon print version of record. 311 $a0-471-79441-4 320 $aIncludes bibliographical references and index. 327 $aDRUG-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) 327 $a1.5.5 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 Pathways 327 $a1.8.3 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 Binding 327 $a2.1.4 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 Interactions 327 $a2.4.1 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; References 327 $a3 Inhibition of Drug-Metabolizing Enzymes and Drug-Drug Interactions in Drug Discovery and Development 330 $aDrug-Drug Interactions in Pharmaceutical Development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage. 410 0$aWiley series in drug discovery and development. 606 $aDrug interactions 606 $aDrug development 615 0$aDrug interactions. 615 0$aDrug development. 676 $a615.7045 676 $a615/.7045 701 $aLi$b A. P$0946693 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910143982103321 996 $aDrug-drug interactions in pharmaceutical development$92138899 997 $aUNINA