LEADER 05631nam 2200769Ia 450 001 9910816078003321 005 20240514073811.0 010 $a1-280-59257-5 010 $a9786613622402 010 $a1-118-18076-3 010 $a1-118-18077-1 010 $a1-118-18074-7 035 $a(CKB)2670000000177367 035 $a(EBL)822074 035 $a(OCoLC)787842596 035 $a(SSID)ssj0000631663 035 $a(PQKBManifestationID)11415164 035 $a(PQKBTitleCode)TC0000631663 035 $a(PQKBWorkID)10599442 035 $a(PQKB)10606429 035 $a(MiAaPQ)EBC822074 035 $a(Au-PeEL)EBL822074 035 $a(CaPaEBR)ebr10560514 035 $a(CaONFJC)MIL362240 035 $a(EXLCZ)992670000000177367 100 $a20110720d2012 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aADME-enabling technologies for drug design and development /$fedited by Donglu Zhang, Sekhar Surapaneni 205 $a1st ed. 210 $aHoboken, N.J. $cWiley$dc2012 215 $a1 online resource (623 p.) 300 $aDescription based upon print version of record. 311 $a0-470-54278-0 320 $aIncludes bibliographical references and index. 327 $aADME-Enabling Technologies in Drug Design and Development; CONTENTS; FOREWORD; PREFACE; CONTRIBUTORS; PART A: ADME: OVERVIEW AND CURRENT TOPICS; 1: REGULATORY DRUG DISPOSITION AND NDA PACKAGE INCLUDING MIST; 1.1 INTRODUCTION; 1.2 NONCLINICAL OVERVIEW; 1.3 PK; 1.4 ABSORPTION; 1.5 DISTRIBUTION; 1.5.1 Plasma Protein Binding; 1.5.2 Tissue Distribution; 1.5.3 Lacteal and Placental Distribution Studies; 1.6 METABOLISM; 1.6.1 In vitro Metabolism Studies; 1.6.2 Drug-Drug Interaction Studies; 1.6.3 In vivo Metabolism (ADME) Studies; 1.7 EXCRETION; 1.8 IMPACT OF METABOLISM INFORMATION ON LABELING 327 $a1.9 CONCLUSIONSREFERENCES; 2: OPTIMAL ADME PROPERTIES FOR CLINICAL CANDIDATE AND INVESTIGATIONAL NEW DRUG (IND) PACKAGE; 2.1 INTRODUCTION; 2.2 NCE AND INVESTIGATIONAL NEW DRUG (IND) PACKAGE; 2.3 ADME OPTIMIZATION; 2.3.1 Absorption; 2.3.2 Metabolism; 2.3.3 PK; 2.4 ADME OPTIMIZATION FOR CNS DRUGS; 2.5 SUMMARY; REFERENCES; 3: DRUG TRANSPORTERS IN DRUG INTERACTIONS AND DISPOSITION; 3.1 INTRODUCTION; 3.2 ABC TRANSPORTERS; 3.2.1 Pgp (MDR1, ABCB1); 3.2.2 BCRP (ABCG2); 3.2.3 MRP2 (ABCC2); 3.3 SLC TRANSPORTERS; 3.3.1 OCT1 (SLC22A1) and OCT2 (SLC22A2); 3.3.2 MATE1 (SLC47A1) and MATE2K (SLC47A2) 327 $a3.3.3 OAT1 (SLC22A6) and OAT3 (SLC22A8)3.3.4 OATP1B1 (SLCO1B1, SLC21A6), OATP1B3 (SLCO1B3, SLC21A8), and OATP2B1 (SLCO2B1, SLC21A9); 3.4 IN VITRO ASSAYS IN DRUG DEVELOPMENT; 3.4.1 Considerations for Assessing Candidate Drugs as Inhibitors; 3.4.2 Considerations for Assessing Candidate Drugs as Substrates; 3.4.3 Assay Systems; 3.5 CONCLUSIONS AND PERSPECTIVES; REFERENCES; 4: PHARMACOLOGICAL AND TOXICOLOGICAL ACTIVITY OF DRUG METABOLITES; 4.1 INTRODUCTION; 4.2 ASSESSMENT OF POTENTIAL FOR ACTIVE METABOLITES; 4.2.1 Detection of Active Metabolites during Drug Discovery 327 $a4.2.2 Methods for Assessing and Evaluating the Biological Activity of Metabolite Mixtures4.2.3 Methods for Generation of Metabolites; 4.3 ASSESSMENT OF THE POTENTIAL TOXICOLOGY OF METABOLITES; 4.3.1 Methods to Study the Formation of Reactive Metabolites; 4.3.2 Reactive Metabolite Studies: In vitro; 4.3.3 Reactive Metabolite Studies: In vivo; 4.3.4 Reactive Metabolite Data Interpretation; 4.3.5 Metabolite Contribution to Off-Target Toxicities; 4.4 SAFETY TESTING OF DRUG METABOLITES; 4.5 SUMMARY; REFERENCES 327 $a5: IMPROVING THE PHARMACEUTICAL PROPERTIES OF BIOLOGICS IN DRUG DISCOVERY: UNIQUE CHALLENGES AND ENABLING SOLUTIONS5.1 INTRODUCTION; 5.2 PHARMACOKINETICS; 5.3 METABOLISM AND DISPOSITION; 5.4 IMMUNOGENICITY; 5.5 TOXICITY AND PRECLINICAL ASSESSMENT; 5.6 COMPARABILITY; 5.7 CONCLUSIONS; REFERENCES; 6: CLINICAL DOSE ESTIMATION USING PHARMACOKINETIC/PHARMACODYNAMIC MODELING AND SIMULATION; 6.1 INTRODUCTION; 6.2 BIOMARKERS IN PK AND PD; 6.2.1 PK; 6.2.2 PD; 6.2.3 Biomarkers; 6.3 MODEL-BASED CLINICAL DRUG DEVELOPMENT; 6.3.1 Modeling; 6.3.2 Simulation; 6.3.3 Population Modeling 327 $a6.3.4 Quantitative Pharmacology (QP) and Pharmacometrics 330 $a A comprehensive guide to cutting-edge tools in ADME research The last decade has seen tremendous progress in the development of analytical techniques such as mass spectrometry and molecular biology tools, resulting in important advances in drug discovery, particularly in the area of absorption, distribution, metabolism, and excretion (ADME). ADME-Enabling Technologies in Drug Design and Development focuses on the current state of the art in the field, presenting a comprehensive review of the latest tools for generating ADME data in drug discovery. It examines the broadest possible rang 606 $aDrugs$xDesign 606 $aDrug development 606 $aDrugs$xMetabolism 606 $aPharmaceutical chemistry 606 $aPharmacokinetics 606 $aPharmaceutical technology 615 0$aDrugs$xDesign. 615 0$aDrug development. 615 0$aDrugs$xMetabolism. 615 0$aPharmaceutical chemistry. 615 0$aPharmacokinetics. 615 0$aPharmaceutical technology. 676 $a615.1/9 701 $aZhang$b Donglu$01621376 701 $aSurapaneni$b Sekhar$01720344 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910816078003321 996 $aADME-enabling technologies for drug design and development$94118918 997 $aUNINA