{"product_id":"oral-bioavailability-and-drug-delivery-9781119660651","title":"Oral Bioavailability and Drug Delivery","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cb\u003eORAL BIOAVAILABILITY \u003csmall\u003eAND\u003c\/small\u003e DRUG DELIVERY\u003c\/b\u003e \u003cp\u003e\u003cb\u003eImprove the performance and viability of newly-developed and approved drugs with this crucial guide\u003c\/b\u003e \u003c\/p\u003e\u003cp\u003eBioavailability is the parameter which measures the rate and extent to which a drug reaches a user's circulatory system depending on the method of administration. For example, intravenous administration produces a bioavailability of 100%, since the drugs are injected directly into the circulatory system; in the case of oral administration, however, bioavailability can vary widely based on factors which, if not properly understood, can result in a failure in drug development, adverse effects, and other complications. The mechanics of oral bioavailability are therefore critical aspects of drug development. \u003c\/p\u003e\u003cp\u003e\u003ci\u003eOral Bioavailability and Drug Delivery\u003c\/i\u003e provides a comprehensive coverage of this subject as well as its drug development applications. Beginning with basic terminology and fundamental concepts, it provide\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003c\/p\u003e\u003cp\u003eList of Contributors xxix\u003c\/p\u003e \u003cp\u003eForeword xxxix\u003c\/p\u003e \u003cp\u003ePreface xli\u003cbr\u003e\u003cbr\u003e \u003cb\u003e1 Barriers to Oral Bioavailability – An Overview 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMing Hu and Xiaoling li\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 1\u003c\/p\u003e \u003cp\u003eReferences 4\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Solubility of Pharmaceutical Solids 5\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePramila Sharma, Yi Gao, Heran li, Bhaskara R. Jasti, Sanming li, and Xiaoling li\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 5\u003c\/p\u003e \u003cp\u003e2.2 Fundamentals of Solubility 6\u003c\/p\u003e \u003cp\u003e2.3 Solubility and Oral Bioavailability 19\u003c\/p\u003e \u003cp\u003e2.4 Strategies to Improve Solubility 21\u003c\/p\u003e \u003cp\u003e2.5 Summary 24\u003c\/p\u003e \u003cp\u003eAbbreviations 25\u003c\/p\u003e \u003cp\u003eReferences 25\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 In Vitro Dissolution of Pharmaceutical Solids 31\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eTze Ning Hiew and Paul W.S. Heng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Dissolution Theory and Fundamentals 31\u003c\/p\u003e \u003cp\u003e3.2 Dissolution of Drug Products 34\u003c\/p\u003e \u003cp\u003e3.3 In Vitro Dissolution Methods for Ensuring Quality of Commercial Drug Products 36\u003c\/p\u003e \u003cp\u003e3.4 In Vitro Dissolution Methods in Product Development 38\u003c\/p\u003e \u003cp\u003e3.5 Automation in Dissolution Testing and Prediction 40\u003c\/p\u003e \u003cp\u003e3.6 Conclusions 42\u003c\/p\u003e \u003cp\u003eReferences 42\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Biological and Physiological Features of the Gastrointestinal Tract Relevant to Oral Drug Absorption 47\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePaul C.L. Ho\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 47\u003c\/p\u003e \u003cp\u003e4.2 Biological Features of Gastrointestinal Tract 47\u003c\/p\u003e \u003cp\u003e4.3 Physiological Features of Gastrointestinal Tract 51\u003c\/p\u003e \u003cp\u003e4.4 Other Physiological Factors 54\u003c\/p\u003e \u003cp\u003e4.5 Conclusion 56\u003c\/p\u003e \u003cp\u003eReferences 56\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Absorption of Drugs Via Passive Diffusion and Carrier-Mediated Pathways 61\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAmit Kokate, Jae H. Chang, and Miki S. Park\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eDisclaimer 61\u003c\/p\u003e \u003cp\u003e5.1 Introduction 61\u003c\/p\u003e \u003cp\u003e5.2 Passive Diffusion 62\u003c\/p\u003e \u003cp\u003e5.3 Carrier-Mediated Transport 67\u003c\/p\u003e \u003cp\u003e5.4 Summary 75\u003c\/p\u003e \u003cp\u003eReferences 75\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Determinant Factors for Passive Absorption of Drugs 79\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eWei Zhu and Mikolaj Milewski\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 79\u003c\/p\u003e \u003cp\u003e6.2 Fundamentals of Drug Absorption 79\u003c\/p\u003e \u003cp\u003e6.3 Absorption Determining Factors 82\u003c\/p\u003e \u003cp\u003e6.4 Rate Limiting Steps in Absorption and Prediction of Dosing Amount Absorbed 86\u003c\/p\u003e \u003cp\u003e6.5 Overview of In Silico Prediction of Absorption and Pharmacokinetics for Oral Dosage Forms 88\u003c\/p\u003e \u003cp\u003e6.6 Summary 89\u003c\/p\u003e \u003cp\u003eReferences 90\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Protein Binding and Drug Distribution 95\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHaiAn Zheng and Marcel Musteata\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 95\u003c\/p\u003e \u003cp\u003e7.2 Protein–Drug Binding in Plasma 95\u003c\/p\u003e \u003cp\u003e7.3 Modeling of Binding Equilibria 97\u003c\/p\u003e \u003cp\u003e7.4 Bioanalytical Methods for Studying Drug–Protein Binding 98\u003c\/p\u003e \u003cp\u003e7.5 Impact of Drug–Protein Binding on Pharmacokinetic Parameters 105\u003c\/p\u003e \u003cp\u003e7.6 Physicochemical Factors that Affect Protein–Drug Binding and Drug Distribution 106\u003c\/p\u003e \u003cp\u003e7.7 Physiological and Pathological Factors that Affect Protein–Drug Binding and Drug Distribution 107\u003c\/p\u003e \u003cp\u003eReferences 107\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Drug Transport Across the Placental Barrier 111\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eValentina Bryant, Mansi Shah, Jennifer Waltz, and Erik Rytting\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 111\u003c\/p\u003e \u003cp\u003e8.2 Pharmacokinetics of Drugs Administered During Pregnancy 111\u003c\/p\u003e \u003cp\u003e8.3 Placental Development and Structure 112\u003c\/p\u003e \u003cp\u003e8.4 Functions of the Human Placenta 113\u003c\/p\u003e \u003cp\u003e8.5 Mechanisms of Drug Transport Across the Placenta 114\u003c\/p\u003e \u003cp\u003e8.6 Mechanisms of Drug Metabolism Within the Placenta 116\u003c\/p\u003e \u003cp\u003e8.7 Strategies to Alter Drug Transport Across the Placenta 117\u003c\/p\u003e \u003cp\u003e8.8 Experimental Models of the Human Placenta 118\u003c\/p\u003e \u003cp\u003eReferences 122\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Biopharmaceutics Classification System: Theory and Practice 131\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMehul Mehta, Jayabharathi Vaidyanathan, and Lawrence Yu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 131\u003c\/p\u003e \u003cp\u003e9.2 Theory 131\u003c\/p\u003e \u003cp\u003e9.3 BCS-based Biowaiver 134\u003c\/p\u003e \u003cp\u003e9.4 BCS Waiver Case Studies 136\u003c\/p\u003e \u003cp\u003e9.5 BCS: Additional Regulatory Applications 138\u003c\/p\u003e \u003cp\u003e9.6 Summary 138\u003c\/p\u003e \u003cp\u003eReferences 139\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Effects of Food on Drug Absorption 141\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eZhu Zhou, Venugopal P. Marasanapalle, Xiaoling Li, and Bhaskara R. Jasti\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 141\u003c\/p\u003e \u003cp\u003e10.2 Mechanisms of Food Effects 147\u003c\/p\u003e \u003cp\u003e10.3 Prediction of Food Effects 149\u003c\/p\u003e \u003cp\u003e10.4 Summary 149\u003c\/p\u003e \u003cp\u003eAbbreviations 150\u003c\/p\u003e \u003cp\u003eReferences 150\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Drug Metabolism in Gastrointestinal Tract 155\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRashim Singh, Dinh Bui, and Ming Hu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 155\u003c\/p\u003e \u003cp\u003e11.2 Role of Intestinal Efflux Transporters in the Drug Disposition 161\u003c\/p\u003e \u003cp\u003e11.3 Drug Metabolism–Transporter Coupling in Drug Disposition in GIT 163\u003c\/p\u003e \u003cp\u003e11.4 Factors Affecting Intestinal Drug Metabolism 168\u003c\/p\u003e \u003cp\u003e11.5 Biopharmaceutics Drug Disposition Classification System 170\u003c\/p\u003e \u003cp\u003e11.6 Metabolism-Based Drug–Drug and Drug–Natural Product Interactions 171\u003c\/p\u003e \u003cp\u003e11.7 Metabolic Interactions Between Gut Microbiome and Drugs in GIT 173\u003c\/p\u003e \u003cp\u003e11.8 Metabolism-Based Xenobiotic-Induced Toxicity 174\u003c\/p\u003e \u003cp\u003e11.9 GIT Metabolism-Based Drug-Designing and Lead Optimization in Drug Development 174\u003c\/p\u003e \u003cp\u003e11.10 Summary 175\u003c\/p\u003e \u003cp\u003eAbbreviations 176\u003c\/p\u003e \u003cp\u003eReferences 176\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Liver Drug Metabolism 189\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eRitika Kurian, Leslie T. Steen, and Hongbing Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 189\u003c\/p\u003e \u003cp\u003e12.2 Hepatic Structure and Function 189\u003c\/p\u003e \u003cp\u003e12.3 Phase I Drug Metabolism 191\u003c\/p\u003e \u003cp\u003e12.4 Phase II Drug Metabolism 199\u003c\/p\u003e \u003cp\u003e12.5 Novel Platforms for Drug Metabolism Studies 204\u003c\/p\u003e \u003cp\u003e12.6 Drug Metabolism and Its Impact on Adverse Drug Reactions 205\u003c\/p\u003e \u003cp\u003e12.7 Conclusion 207\u003c\/p\u003e \u003cp\u003eReferences 207\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Urinary Excretion of Drugs and Drug Reabsorption 213\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJessica T. Babic, Jack Cook, and Vincent H. Tam\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 213\u003c\/p\u003e \u003cp\u003e13.2 Kidney as an Eliminating Organ 213\u003c\/p\u003e \u003cp\u003e13.3 Drug Transporters and Their Role in Renal Elimination 220\u003c\/p\u003e \u003cp\u003e13.4 Renal Elimination and Bioavailability 222\u003c\/p\u003e \u003cp\u003e13.5 Augmented Renal Clearance 227\u003c\/p\u003e \u003cp\u003eReferences 228\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Excretion of Drugs and Their Metabolites into the Bile 233\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eSong Gao, Imoh Etim, Robin Sunsong, Christabel Ebuzoeme, Ting Du, and Dinh Bui\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 233\u003c\/p\u003e \u003cp\u003e14.2 Anatomy and Physiology of the Liver and Biliary System 234\u003c\/p\u003e \u003cp\u003e14.3 Biliary Excreted Drugs and Metabolites 235\u003c\/p\u003e \u003cp\u003e14.4 Impact of Biliary Excretion on ADME and Pharmacokinetics 235\u003c\/p\u003e \u003cp\u003e14.5 Hepatic Transporters Involved in Biliary Excretion 245\u003c\/p\u003e \u003cp\u003e14.6 Factors Affecting Biliary Secretion 248\u003c\/p\u003e \u003cp\u003e14.7 Biliary Excretion Research Models 250\u003c\/p\u003e \u003cp\u003e14.8 Concluding Remarks 255\u003c\/p\u003e \u003cp\u003eAbbreviations 255\u003c\/p\u003e \u003cp\u003eReferences 255\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Pharmacokinetic Behaviors of Orally Administered Drugs 267\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHamdah Al Nebaihi, Dion R. Brocks, Jaime A. Yáñez, Marcus Laird Forrest, and Neal M. Davies\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eObjectives 267\u003c\/p\u003e \u003cp\u003e15.1 Introduction 267\u003c\/p\u003e \u003cp\u003e15.2 Physicochemical Factors Affecting Oral Concentration Time Profiles 274\u003c\/p\u003e \u003cp\u003e15.3 Physiological Factors Affecting Oral Concentration Time Profiles 281\u003c\/p\u003e \u003cp\u003e15.4 Food-Effects and Oral Concentration Time Profiles 296\u003c\/p\u003e \u003cp\u003e15.5 The Impact of the Lymphatic System on Oral Bioavailability 298\u003c\/p\u003e \u003cp\u003e15.6 Summation 303\u003c\/p\u003e \u003cp\u003eAbbreviations 304\u003c\/p\u003e \u003cp\u003eReferences 304\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 In Vitro-In Vivo Correlations of Pharmaceutical Dosage Forms 315\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eDeliang Zhou and Yihong Qiu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 315\u003c\/p\u003e \u003cp\u003e16.2 Categories of In Vitro-In Vivo Correlations 316\u003c\/p\u003e \u003cp\u003e16.3 Convolution and Deconvolution 317\u003c\/p\u003e \u003cp\u003e16.4 Development and Assessments of an IVIVC 321\u003c\/p\u003e \u003cp\u003e16.5 Applications of an IVIVC 324\u003c\/p\u003e \u003cp\u003e16.6 Challenges 325\u003c\/p\u003e \u003cp\u003e16.7 Physiologically Based Biopharmaceutics Models (PBBM) 326\u003c\/p\u003e \u003cp\u003e16.8 Summary 328\u003c\/p\u003e \u003cp\u003eReferences 329\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Advanced Concepts in Oral Bioavailability Research – An Overview 333\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eBaojian Wu, Min Chen, and Ming Hu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eAbbreviations 336\u003c\/p\u003e \u003cp\u003eReferences 336\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Expression and Pharmaceutical Relevance of Intestinal Transporters 339\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMelanie A. Felmlee, Michael Ng, and Annie Lee\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 339\u003c\/p\u003e \u003cp\u003e18.2 Intestinal Drug Transport 340\u003c\/p\u003e \u003cp\u003e18.3 Uptake Transporters 341\u003c\/p\u003e \u003cp\u003e18.4 Efflux Transporters 350\u003c\/p\u003e \u003cp\u003e18.5 Summary 353\u003c\/p\u003e \u003cp\u003eReferences 353\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19 Amino Acid Transporters 361\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLiping Wang, Xiaoyan Li, Mengdi Ying, Ming Hu, and Zhongqiu Liu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 361\u003c\/p\u003e \u003cp\u003e19.2 Classification of Amino Acid Transporters and their Functions 364\u003c\/p\u003e \u003cp\u003e19.3 Epithelial Amino Acid Transporters 372\u003c\/p\u003e \u003cp\u003e19.4 Endothelial Amino Acid Transporters 378\u003c\/p\u003e \u003cp\u003e19.5 Regulation of Amino Acid Transport 380\u003c\/p\u003e \u003cp\u003e19.6 Conclusion 382\u003c\/p\u003e \u003cp\u003eAbbreviations 382\u003c\/p\u003e \u003cp\u003eReferences 383\u003c\/p\u003e \u003cp\u003e\u003cb\u003e20 Drug Transporters and Their Role in Absorption and Disposition of Peptides and Peptide-Based Pharmaceuticals 393\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eDavid J. Lindley, Stephen M. Carl, Dea Herrera-Ruiz, Li F. Pan, Lori B. Ward, Jonathan M.E. Goole, Olafur S. Gudmundsson, Matthew Behymer, and Gregory T. Knipp\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction 393\u003c\/p\u003e \u003cp\u003e20.2 Transport Systems Mediating Peptide-based Pharmaceutical Absorption and Disposition: The Solute Carrier (SLC) Family 397\u003c\/p\u003e \u003cp\u003e20.3 ATP Binding Cassette (ABC) Transporters 399\u003c\/p\u003e \u003cp\u003e20.4 Gastrointestinal Tract-Specific Transporter Activity 400\u003c\/p\u003e \u003cp\u003e20.5 Conclusions 407\u003c\/p\u003e \u003cp\u003eAcknowledgments 408\u003c\/p\u003e \u003cp\u003eReferences 408\u003c\/p\u003e \u003cp\u003e\u003cb\u003e21 OATP Transporters in Hepatic and Intestinal Uptake of Orally Administered Drugs 417\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eWei Yue, Taleah Farasyn, Alexandra Crowe, Khondoker Alam, Lucila Garcia-Contreras, Yifan Tu, and Lu Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e21.1 Introduction 417\u003c\/p\u003e \u003cp\u003e21.2 Hepatic OATP1B1 and OATP1B 3 417\u003c\/p\u003e \u003cp\u003e21.3 OATP2B1 in the Intestine 420\u003c\/p\u003e \u003cp\u003e21.4 OATP1A2 in the intestine 421\u003c\/p\u003e \u003cp\u003e21.5 Summary 422\u003c\/p\u003e \u003cp\u003eAcknowledgement 422\u003c\/p\u003e \u003cp\u003eReferences 422\u003c\/p\u003e \u003cp\u003e\u003cb\u003e22 ABC Transporters in Intestinal and Liver Efflux 429\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMarilyn E. Morris and Tianjing Ren\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e22.1 Introduction 429\u003c\/p\u003e \u003cp\u003e22.2 Apical Membrane Efflux Proteins 430\u003c\/p\u003e \u003cp\u003e22.3 Basolateral\/Lateral Membrane Efflux Proteins 442\u003c\/p\u003e \u003cp\u003e22.4 Clinical Relevance of ABC Transporters in Oral Bioavailability of Drugs 444\u003c\/p\u003e \u003cp\u003e22.5 Pharmacogenomics of ABC Transporters 445\u003c\/p\u003e \u003cp\u003e22.6 Regulation of Efflux Transporters 445\u003c\/p\u003e \u003cp\u003e22.7 Summary 446\u003c\/p\u003e \u003cp\u003eAbbreviations 446\u003c\/p\u003e \u003cp\u003eAcknowledgments 447\u003c\/p\u003e \u003cp\u003eReferences 447\u003c\/p\u003e \u003cp\u003e\u003cb\u003e23 Interplay Between Metabolic Enzymes and Transporters 455\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eZuoxu Xie, Lu Wang, Zicong Zheng, Yifan Tu, Yi Rong, Ming Hu, and Stephen Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e23.1 Pathways and Functions of Drug Metabolic Enzymes and Transporters 455\u003c\/p\u003e \u003cp\u003e23.2 Interplay Between Metabolic Enzymes and Transporters 462\u003c\/p\u003e \u003cp\u003e23.3 Conclusion 467\u003c\/p\u003e \u003cp\u003eReferences 468\u003c\/p\u003e \u003cp\u003e\u003cb\u003e24 Systemic Versus Local Bioavailability Enabled by Recycling 473\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYifan Tu, Lu Wang, and Ming Hu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e24.1 Introduction 473\u003c\/p\u003e \u003cp\u003e24.2 Systemic Bioavailability 473\u003c\/p\u003e \u003cp\u003e24.3 Local Bioavailability 474\u003c\/p\u003e \u003cp\u003e24.4 Factors Affecting Bioavailability 474\u003c\/p\u003e \u003cp\u003e24.5 Enterohepatic Recycling (EHR) 475\u003c\/p\u003e \u003cp\u003e24.6 Hepatoenteric Recycling (HER) 479\u003c\/p\u003e \u003cp\u003e24.7 Enteroenteric Recycling (EER) 480\u003c\/p\u003e \u003cp\u003e24.8 Summary 480\u003c\/p\u003e \u003cp\u003eReferences 480\u003c\/p\u003e \u003cp\u003e\u003cb\u003e25 Intestinal Microbiome and Its Impact on Metabolism and Safety of Drugs 483\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eXin Y. Chu and Paul C.L. Ho\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e25.1 Introduction 483\u003c\/p\u003e \u003cp\u003e25.2 Direct Metabolism by Intestinal Microbiome 483\u003c\/p\u003e \u003cp\u003e25.3 Indirect Mechanisms Affecting Drug Metabolism 489\u003c\/p\u003e \u003cp\u003e25.4 Impact of Intestinal Microbiome on Drug Treatment in Clinical Practice 492\u003c\/p\u003e \u003cp\u003e25.5 Conclusion and Future Perspectives 492\u003c\/p\u003e \u003cp\u003eReferences 493\u003c\/p\u003e \u003cp\u003e\u003cb\u003e26 Drug–Drug Interactions and Drug–Dietary Chemical Interactions 501\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMengbi Yang, Yuanfeng Lyu, and Zhong Zuo\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e26.1 Introduction 501\u003c\/p\u003e \u003cp\u003e26.2 Drug–Drug Interactions (DDIs) 501\u003c\/p\u003e \u003cp\u003e26.3 Drug–Dietary Chemical Interactions in Oral Bioavailability 510\u003c\/p\u003e \u003cp\u003e26.4 Summary 517\u003c\/p\u003e \u003cp\u003eAbbreviations 517\u003c\/p\u003e \u003cp\u003eReferences 518\u003c\/p\u003e \u003cp\u003e\u003cb\u003e27 Regulatory Considerations in Metabolism- and Transport-Based Drug Interactions 523\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eXinning Yang, Sue-Chih Lee, Xinyuan Zhang, and Lei Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eDisclaimer 523\u003c\/p\u003e \u003cp\u003e27.1 Overview of Drug–Drug Interactions 523\u003c\/p\u003e \u003cp\u003e27.2 Regulatory Recommendations of DDI Studies 527\u003c\/p\u003e \u003cp\u003e27.3 Highlights of the Final Guidances for Industry: In Vitro and Clinical Drug Interaction Studies – Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions 528\u003c\/p\u003e \u003cp\u003e27.4 Role of Physiologically Based Pharmacokinetic (PBPK) Modeling in DDI Assessment 544\u003c\/p\u003e \u003cp\u003e27.5 A Labeling Example to Illustrate the Translation of Complicated Drug Interaction Results to Labeling: Tipranavir 547\u003c\/p\u003e \u003cp\u003e27.6 Examples to Illustrate the Use of PBPK in Supporting Labeling for Drugs that are Dual CYP3A\/P-GP Substrates 549\u003c\/p\u003e \u003cp\u003e27.7 Summary 549\u003c\/p\u003e \u003cp\u003eAcknowledgement 550\u003c\/p\u003e \u003cp\u003eReferences 550\u003c\/p\u003e \u003cp\u003e\u003cb\u003e28 Formulation Approaches to Improve Oral Bioavailability of Drugs 559\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eZeren Wang, Chandan Bhugra, and Shun Chen\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e28.1 Introduction 559\u003c\/p\u003e \u003cp\u003e28.2 Theoretical Considerations for Formulation Development of Poorly Water-Soluble Drugs 560\u003c\/p\u003e \u003cp\u003e28.3 Formulation Considerations for the Development of Poorly Water-Soluble Drugs 563\u003c\/p\u003e \u003cp\u003e28.4 Other Formulation Approaches 571\u003c\/p\u003e \u003cp\u003eReferences 571\u003c\/p\u003e \u003cp\u003e\u003cb\u003e29 Lipid-Based and Self-Emulsifying Oral Drug Delivery Systems 575\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePushkaraj Wagh, Jonathan Moreno, Christopher Nayar, and Jeffrey Wang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e29.1 Introduction 575\u003c\/p\u003e \u003cp\u003e29.2 Lipid-based Drug Delivery Systems 575\u003c\/p\u003e \u003cp\u003e29.3 Advantages and Limitations of Lipid-Based and Self-Emulsifying Drug Delivery Systems 586\u003c\/p\u003e \u003cp\u003e29.4 Summary 586\u003c\/p\u003e \u003cp\u003eReferences 586\u003c\/p\u003e \u003cp\u003e\u003cb\u003e30 Oral Delivery of Nanoparticles: Challenges and Opportunities 591\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eQing Lin, Ling Zhang, and Zhirong Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e30.1 Introduction 591\u003c\/p\u003e \u003cp\u003e30.2 Role of Nanoparticle Shape, Size, and Surface in Oral Delivery of Nanoparticles 592\u003c\/p\u003e \u003cp\u003e30.3 Characterization Methods of Nanoparticles for Oral Delivery 593\u003c\/p\u003e \u003cp\u003e30.4 State-of-the-Art Carriers Designed and Applied in Oral Delivery of Nanoparticles 594\u003c\/p\u003e \u003cp\u003e30.5 Challenges and Coexisting Opportunities 594\u003c\/p\u003e \u003cp\u003eReferences 595\u003c\/p\u003e \u003cp\u003e\u003cb\u003e31 Oral Delivery of Therapeutic Peptides: Strategies for Product Development 599\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePuchun Liu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e31.1 Introduction 599\u003c\/p\u003e \u003cp\u003e31.2 Overview of Approaches to Enabling Oral Peptide Delivery 604\u003c\/p\u003e \u003cp\u003e31.3 Observation and Data Analysis of Low BA with Large Variabilities 607\u003c\/p\u003e \u003cp\u003e31.4 Recommended Strategies for Oral Peptide Product Development 609\u003c\/p\u003e \u003cp\u003eAbbreviations 613\u003c\/p\u003e \u003cp\u003eReferences 613\u003c\/p\u003e \u003cp\u003e\u003cb\u003e32 Prodrugs to Improve Oral Delivery 619\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eArjun D. Patel, Shuchi Gupta, and Mamoun Alhamadsheh\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e32.1 Introduction 619\u003c\/p\u003e \u003cp\u003e32.2 Factors Associated With Oral Drug Absorption 620\u003c\/p\u003e \u003cp\u003e32.3 Intestinal Physiology and Background 620\u003c\/p\u003e \u003cp\u003e32.4 Strategies to Improve the Bioavailability of Orally Administered Drugs 621\u003c\/p\u003e \u003cp\u003e32.5 Prodrug Overview and Classification 622\u003c\/p\u003e \u003cp\u003e32.6 Prodrug Strategies to Improve Aqueous Solubility 630\u003c\/p\u003e \u003cp\u003e32.7 Prodrug Approaches for Enhancing Absorption 631\u003c\/p\u003e \u003cp\u003e32.8 Prodrug Approaches for Targeting Enzymes 631\u003c\/p\u003e \u003cp\u003e32.9 Prodrug Approaches for Targeting Membrane Transporters 632\u003c\/p\u003e \u003cp\u003e32.10 Conclusion 633\u003c\/p\u003e \u003cp\u003eAbbreviations 634\u003c\/p\u003e \u003cp\u003eReferences 634\u003c\/p\u003e \u003cp\u003e\u003cb\u003e33 Gastroretentive Drug Delivery Systems 637\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eVrushali Waknis and Ajit S. Narang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e33.1 Introduction 637\u003c\/p\u003e \u003cp\u003e33.2 Oral Drug Delivery – Challenges and Opportunities 637\u003c\/p\u003e \u003cp\u003e33.3 Human Gastric Physiology Relevant to GRDDS Design 638\u003c\/p\u003e \u003cp\u003e33.4 Technologies 639\u003c\/p\u003e \u003cp\u003e33.5 New Drug Development Considerations 645\u003c\/p\u003e \u003cp\u003e33.6 Commercial GRDDS Products and Investigational New Products 649\u003c\/p\u003e \u003cp\u003e33.7 Future Outlook 653\u003c\/p\u003e \u003cp\u003eAcknowledgments 654\u003c\/p\u003e \u003cp\u003eReferences 654\u003c\/p\u003e \u003cp\u003e\u003cb\u003e34 Enhancing Oral Bioavailability Using 3D Printing Technology 657\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eTimothy Tracy, Senping Cheng, Lei Wu, Xin liu, and Xiaoling li\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e34.1 Introduction 657\u003c\/p\u003e \u003cp\u003e34.2 3D Printing in Pharmaceutical Applications 657\u003c\/p\u003e \u003cp\u003e34.3 Novel Tablet Structures Possible with 3D Printing 660\u003c\/p\u003e \u003cp\u003e34.4 Application of 3D Printing in Oral Bioavailability Enhancement 663\u003c\/p\u003e \u003cp\u003e34.5 Future Outlook for 3D Printing and Bioavailability Enhancement 672\u003c\/p\u003e \u003cp\u003e34.6 Summary 673\u003c\/p\u003e \u003cp\u003eReferences 673\u003c\/p\u003e \u003cp\u003e\u003cb\u003e35 Anatomical and Physiological Factors Affecting Oral Drug Bioavailability in Rats, Dogs, Monkeys, and Humans 677\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAyman El-Kattan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e35.1 Introduction 677\u003c\/p\u003e \u003cp\u003e35.2 Determinants of Oral Bioavailability 677\u003c\/p\u003e \u003cp\u003e35.3 Summary 691\u003c\/p\u003e \u003cp\u003eReferences 691\u003c\/p\u003e \u003cp\u003e\u003cb\u003e36 In Vivo Methods for Oral Bioavailability Studies 701\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAna Ruiz-Garcia and Marival Bermejo\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e36.1 Introduction 701\u003c\/p\u003e \u003cp\u003e36.2 Factors that Affect Oral Availability 701\u003c\/p\u003e \u003cp\u003e36.3 In Vivo Animal Techniques 706\u003c\/p\u003e \u003cp\u003e36.4 Animals Used in Bioavailability Studies 706\u003c\/p\u003e \u003cp\u003e36.5 General Considerations for Blood Sampling 708\u003c\/p\u003e \u003cp\u003e36.6 Statistical Considerations for Data Handling. (AUC Calculations in Sparse Sampling Designs) 708\u003c\/p\u003e \u003cp\u003e36.7 Practical Examples in Rat Model 709\u003c\/p\u003e \u003cp\u003e36.8 Intestinal Perfusion (see also Chapter 42) 710\u003c\/p\u003e \u003cp\u003e36.9 Mathematical Considerations 711\u003c\/p\u003e \u003cp\u003eReferences 712\u003c\/p\u003e \u003cp\u003e\u003cb\u003e37 Caco-2 Cell Culture Model for Oral Drug Absorption 715\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eKaustubh Kulkarni, Lu Wang, and Ming Hu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e37.1 Introduction 715\u003c\/p\u003e \u003cp\u003e37.2 Description 717\u003c\/p\u003e \u003cp\u003e37.3 Utility 719\u003c\/p\u003e \u003cp\u003e37.4 Recent Progress 720\u003c\/p\u003e \u003cp\u003e37.5 Significance of Caco-2 Cell Culture Model in Drug Discovery and Development 722\u003c\/p\u003e \u003cp\u003e37.6 Example 722\u003c\/p\u003e \u003cp\u003e37.7 Concluding Remarks 727\u003c\/p\u003e \u003cp\u003eReferences 727\u003c\/p\u003e \u003cp\u003e\u003cb\u003e38 OATP Overexpressed Cells and Their Use in Drug Uptake Studies 729\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLu Wang, Zuoxu Xie, Yifan Tu, and Ming Hu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e38.1 Introduction to OATP Cell Assay 729\u003c\/p\u003e \u003cp\u003e38.2 Materials 731\u003c\/p\u003e \u003cp\u003e38.3 Methods 731\u003c\/p\u003e \u003cp\u003e38.4 Data Analysis 732\u003c\/p\u003e \u003cp\u003e38.5 Notes 733\u003c\/p\u003e \u003cp\u003eReferences 735\u003c\/p\u003e \u003cp\u003e\u003cb\u003e39 Use of Human Intestinal and Hepatic Tissue Fractions and Microbiome as Models in Assessment of Drug Metabolism and its Impact on Oral Bioavailability 737\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eHani Zaher and George Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e39.1 Introduction 737\u003c\/p\u003e \u003cp\u003e39.2 Gastrointestinal Tract and Absorption (see Also Chapter 5) 737\u003c\/p\u003e \u003cp\u003e39.3 Mechanisms of Drug Absorption and Concept of Oral Bioavailability (see also Chapters 4–6) 738\u003c\/p\u003e \u003cp\u003e39.4 Intestinal Metabolism and Oral Bioavailability (see Also Chapter 11) 739\u003c\/p\u003e \u003cp\u003e39.5 In Vitro Systems Applied to Assess Intestinal Metabolism 740\u003c\/p\u003e \u003cp\u003e39.6 In Vitro Systems Applied to Assess Human Hepatic First-Pass Metabolism (see Also Chapter 12) 743\u003c\/p\u003e \u003cp\u003e39.7 Long-Term Hepatocyte Culture and Slow Metabolizing Drug Candidate 745\u003c\/p\u003e \u003cp\u003e39.8 Microbiome and Absorption: A New Perspective 747\u003c\/p\u003e \u003cp\u003e39.9 Summary 748\u003c\/p\u003e \u003cp\u003eAcknowledgments 748\u003c\/p\u003e \u003cp\u003eAbbreviations 749\u003c\/p\u003e \u003cp\u003eReferences 749\u003c\/p\u003e \u003cp\u003e\u003cb\u003e40 Liver Perfusion and Primary Hepatocytes for Studying Drug Metabolism and Metabolite Excretion 757\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eParesh P. Chothe, Sean Xiaochun Zhu, Sandeepraj Pusalkar, Chuang Lu, and Cindy Xia\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e40.1 Introduction 757\u003c\/p\u003e \u003cp\u003e40.2 Liver Perfusion 758\u003c\/p\u003e \u003cp\u003e40.3 Primary Hepatocytes 762\u003c\/p\u003e \u003cp\u003e40.4 Organ Perfusion Versus Hepatocyte Studies 771\u003c\/p\u003e \u003cp\u003e40.5 Perspectives 772\u003c\/p\u003e \u003cp\u003eAcknowledgements 772\u003c\/p\u003e \u003cp\u003eAbbreviations 772\u003c\/p\u003e \u003cp\u003eReferences 772\u003c\/p\u003e \u003cp\u003e\u003cb\u003e41 Determination of Regulation of Drug Metabolizing Enzymes and Transporters 779\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eSergio C. Chai, Taosheng Chen, and Wen Xie\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e41.1 Introduction 779\u003c\/p\u003e \u003cp\u003e41.2 In vivo Methods 779\u003c\/p\u003e \u003cp\u003e41.3 In vitro Methods 784\u003c\/p\u003e \u003cp\u003e41.4 Biochemical, Biophysical and Structural Analysis of NRs Using Purified Proteins 789\u003c\/p\u003e \u003cp\u003e41.5 Conclusions 796\u003c\/p\u003e \u003cp\u003eAcknowledgments 796\u003c\/p\u003e \u003cp\u003eReferences 796\u003c\/p\u003e \u003cp\u003e\u003cb\u003e42 Intestinal Perfusion Methods for Oral Drug Absorptions 801\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eli li, Dinh Bui, Wei Zhu, and Eun-Jung (Zenobia) Jeong\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e42.1 Introduction 801\u003c\/p\u003e \u003cp\u003e42.2 Application and Recent Development of the Intestinal Perfusion Method 801\u003c\/p\u003e \u003cp\u003e42.3 Data Interpretation and Method Comparison 803\u003c\/p\u003e \u003cp\u003e42.4 Common In Vitro Methods Studying Intestinal Permeability and Metabolism 803\u003c\/p\u003e \u003cp\u003e42.5 Summary 807\u003c\/p\u003e \u003cp\u003e42.6 Methodologies and Experimental Data Analysis 807\u003c\/p\u003e \u003cp\u003eAcknowledgment 813\u003c\/p\u003e \u003cp\u003eReferences 815\u003c\/p\u003e \u003cp\u003e\u003cb\u003e43 In Silico Prediction of Oral Drug Absorption 819\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJin Dong, Zhu Zhou, Yujuan Zheng, and Miki Susanto Park\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e43.1 Introduction 819\u003c\/p\u003e \u003cp\u003e43.2 QSPR Modeling 819\u003c\/p\u003e \u003cp\u003e43.3 PBPK Modeling 821\u003c\/p\u003e \u003cp\u003e43.4 PBBM Modeling as a Subset of PBPK Modeling 823\u003c\/p\u003e \u003cp\u003e43.5 Applications of PBPK\/PBBM Modeling 824\u003c\/p\u003e \u003cp\u003e43.6 PBPK Software 827\u003c\/p\u003e \u003cp\u003e43.7 Summary 839\u003c\/p\u003e \u003cp\u003eReferences 839\u003c\/p\u003e \u003cp\u003e\u003cb\u003e44 Computational Modeling of Drug Oral Bioavailability 843\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLon W.R. Fong, Beibei Huang, Rajan Chaudhari, and Shuxing Zhang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e44.1 Introduction 843\u003c\/p\u003e \u003cp\u003e44.2 Computational Modeling of Bioavailability 844\u003c\/p\u003e \u003cp\u003e44.3 Conclusions 851\u003c\/p\u003e \u003cp\u003eAcknowledgment 852\u003c\/p\u003e \u003cp\u003eReferences 852\u003c\/p\u003e \u003cp\u003e\u003cb\u003e45 Blood–Brain Barrier Permeability Assessment for Small-Molecule Drug Discovery Using Computational Techniques 857\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYankang Jing and Xiang-Qun Xie\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e45.1 Introduction 857\u003c\/p\u003e \u003cp\u003e45.2 Basic Principle of the BBB Permeation 857\u003c\/p\u003e \u003cp\u003e45.3 Role of the BBB in Drug Delivery 858\u003c\/p\u003e \u003cp\u003e45.4 Experimental Methods for Assessing BBB Permeability 858\u003c\/p\u003e \u003cp\u003e45.5 Computational Method to Predict BBB Permeability 859\u003c\/p\u003e \u003cp\u003eAbbreviations 867\u003c\/p\u003e \u003cp\u003eReferences 867\u003c\/p\u003e \u003cp\u003eIndex 871\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49407112446295,"sku":"9781119660651","price":212.4,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119660651.jpg?v=1730498220","url":"https:\/\/bookcurl.com\/products\/oral-bioavailability-and-drug-delivery-9781119660651","provider":"Book Curl","version":"1.0","type":"link"}