LEADER 05422nam 22006734a 450 001 9910143981703321 005 20170815121018.0 010 $a1-281-09423-4 010 $a9786611094232 010 $a0-470-19169-4 010 $a0-470-19168-6 035 $a(CKB)1000000000376121 035 $a(EBL)319292 035 $a(OCoLC)476116011 035 $a(SSID)ssj0000141567 035 $a(PQKBManifestationID)11147365 035 $a(PQKBTitleCode)TC0000141567 035 $a(PQKBWorkID)10056730 035 $a(PQKB)10235519 035 $a(MiAaPQ)EBC319292 035 $a(PPN)240481968 035 $a(EXLCZ)991000000000376121 100 $a20070427d2008 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aDrug metabolism in drug design and development$b[electronic resource] $ebasic concepts and practice /$fedited by Donglu Zhang, Mingshe Zhu, W. Griffith Humphreys 210 $aHoboken, N.J. $cWiley-Interscience$dc2008 215 $a1 online resource (633 p.) 300 $aDescription based upon print version of record. 311 $a0-471-73313-X 320 $aIncludes bibliographical references and index. 327 $aDRUG METABOLISM IN DRUG DESIGN AND DEVELOPMENT; CONTENTS; Preface; Contributors; PART I BASIC CONCEPTS OF DRUG METABOLISM; 1 Overview: Drug Metabolism in the Modern Pharmaceutical Industry; 1.1 Introduction; 1.2 Technology; 1.3 Breadth of Science; 1.3.1 Chemistry; 1.3.2 Enzymology and Molecular Biology; 1.4 Impact of Drug Metabolism on Efficacy and Safety; 1.4.1 Efficacy; 1.4.2 Safety; 1.5 Regulatory Impact and IP Position; 1.6 Summary; References; 2 Oxidative, Reductive, and Hydrolytic Metabolism of Drugs; 2.1 Introduction; 2.2 Nomenclature and Terminology 327 $a2.3 General Features of the Enzymes2.4 Fractional Contributions of Different Enzymes; 2.5 Oxidation Enzymes; 2.5.1 Cytochrome P450 (P450, CYP); 2.5.2 Flavin-Containing Monooxygenase (FMO); 2.5.3 Monoamine Oxidase (MAO); 2.5.4 Aldehyde Oxidase and Xanthine Dehydrogenase; 2.5.5 Peroxidases; 2.5.6 Alcohol Dehydrogenases (ADH); 2.5.7 Aldehyde Dehydrogenases (ALDH); 2.6 Reduction; 2.6.1 P450, ADH; 2.6.2 NADPH-P450 Reductase; 2.6.3 Aldo-Keto Reductases (AKR); 2.6.4 Quinone Reductase (NQO); 2.6.5 Glutathione Peroxidase (GPX); 2.7 Hydrolysis; 2.7.1 Epoxide Hydrolase; 2.7.2 Esterases and Amidases 327 $a2.8 SummaryReferences; 3 Conjugative Metabolism of Drugs; 3.1 UDP-Glucuronosyltransferases; 3.1.1 Location Within the Cell; 3.1.2 Endogenous Substrates; 3.1.3 Enzyme Multiplicity; 3.1.4 Inducibility; 3.1.5 Pharmacogenetics; 3.1.6 Experimental Considerations; 3.1.7 Enzyme Selective Substrates and Inhibitors; 3.1.8 Drug-Drug Interactions and Glucuronidation; 3.1.9 Summary; 3.2 Cytosolic Sulfotransferases; 3.2.1 Cellular Location and Tissue Expression; 3.2.2 The SULT Superfamily of Cytosolic Enzymes; 3.2.3 Inducibility; 3.2.4 SULT Pharmacogenetics 327 $a3.2.5 Analytical Detection of Sulfonated Metabolites3.2.6 SULT Inhibitors (Pacifici and Coughtrie, 2005); 3.2.7 Drug-Drug Interactions and Sulfonation; 3.2.8 Summary; 3.3 Glutathione-S-Transferases; 3.3.1 General Overview; 3.3.2 Classification of the GST Enzymes; 3.3.3 Localization and Expression; 3.3.4 Reactions Catalyzed by GSTs; 3.3.5 Regulation of GSTs; 3.3.6 GST Alpha Class; 3.3.7 GST Mu Class; 3.3.8 GST Pi Class; 3.3.9 GST Theta Class; 3.3.10 GST Zeta Class; 3.3.11 Incubation Conditions and Analytical Methods; 3.3.12 Glutathione Conjugate Metabolism (Mercapturic Acid Pathway) 327 $aReferences4 Enzyme Kinetics; 4.1 Introduction; 4.2 Enzyme Catalysis; 4.3 Michaelis-Menten Kinetics; 4.3.1 Meanings of K(m), V(max) and Their Clinical Relevance; 4.4 Graphical Kinetic Plots; 4.5 Atypical Kinetics-Allosteric Effects; 4.5.1 Overview of Atypical Kinetic Phenomena; 4.5.2 Homotropic Cooperativity; 4.5.3 Heterotropic Cooperativity; 4.6 Graphical Analysis of Atypical Kinetic Data; 4.7 Enzyme Inhibition Kinetics; 4.7.1 Overview; 4.7.2 Competitive Inhibition; 4.7.3 Mixed Inhibition; 4.7.4 Noncompetitive Inhibition; 4.7.5 Uncompetitive Inhibition 327 $a4.7.6 Summary of Effects of Various Inhibition Types of Kinetic Parameters 330 $aThe essentials of drug metabolism vital to developing new therapeutic entitiesInformation on the metabolism and disposition of candidate drugs is a critical part of all aspects of the drug discovery and development process. Drug metabolism, as practiced in the pharmaceutical industry today, is a complex, multidisciplinary field that requires knowledge of sophisticated analytical technologies and expertise in mechanistic and kinetic enzymology, organic reaction mechanism, pharmacokinetic analysis, animal physiology, basic chemical toxicology, preclinical pharmacology, and molecular biol 606 $aDrugs$xMetabolism 606 $aDrugs$xDesign 606 $aDrug development 615 0$aDrugs$xMetabolism. 615 0$aDrugs$xDesign. 615 0$aDrug development. 676 $a615.7 676 $a615/.7 701 $aZhang$b Donglu$0874045 701 $aZhu$b Mingshe$0874046 701 $aHumphreys$b W. Griffith$0874047 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910143981703321 996 $aDrug metabolism in drug design and development$91951506 997 $aUNINA