{"product_id":"oral-bioavailability-and-drug-delivery-isbn-9781119660651","title":"Oral Bioavailability and Drug Delivery","description":"\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 provides a thorough understanding of the challenges and barriers to oral bioavailability as well as the possibilities for improving this parameter. The resulting book is an indispensable tool for drug development research. \u003c\/p\u003e\u003cp\u003e\u003ci\u003eOral Bioavailability and Drug Delivery\u003c\/i\u003e readers will also find: \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eDiscussion questions in many chapters to facilitate comprehension\u003c\/li\u003e \u003cli\u003eDetailed discussion of topics including dissolution, absorption, metabolism, and more\u003c\/li\u003e \u003cli\u003eReal-world examples of methods in actions throughout\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003e\u003ci\u003eOral Bioavailability and Drug Delivery\u003c\/i\u003e is ideal for pharmaceutical and biotechnology scientists working in drug discovery and development; researchers in chemistry, biology, pharmacology, immunology, neuroscience, and other related fields; and graduate courses in drug development and delivery. \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  \u003cp\u003e\u003cb\u003eMing Hu, PhD,\u003c\/b\u003e is Professor of Pharmaceutics at the College of Pharmacy, University of Houston, Texas, USA. \u003c\/p\u003e\u003cp\u003e\u003cb\u003eXiaoling Li, PhD,\u003c\/b\u003e is Professor of Pharmaceutics at the TJL School of Pharmacy, University of the Pacific, California, USA.   \u003c\/p\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 provides a thorough understanding of the challenges and barriers to oral bioavailability as well as the possibilities for improving this parameter. The resulting book is an indispensable tool for drug development research. \u003c\/p\u003e\u003cp\u003e\u003ci\u003eOral Bioavailability and Drug Delivery\u003c\/i\u003e readers will also find: \u003c\/p\u003e\u003cul\u003e\n\u003cli\u003eDiscussion questions in many chapters to facilitate comprehension\u003c\/li\u003e \u003cli\u003eDetailed discussion of topics including dissolution, absorption, metabolism, and more\u003c\/li\u003e \u003cli\u003eReal-world examples of methods in actions throughout\u003c\/li\u003e\n\u003c\/ul\u003e \u003cp\u003e\u003ci\u003eOral Bioavailability and Drug Delivery\u003c\/i\u003e is ideal for pharmaceutical and biotechnology scientists working in drug discovery and development; researchers in chemistry, biology, pharmacology, immunology, neuroscience, and other related fields; and graduate courses in drug development and delivery.\u003c\/p\u003e","brand":"Wiley","offers":[{"title":"Default Title","offer_id":47989724741861,"sku":"NP9781119660651","price":295.0,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9781119660651.jpg?v=1761785257","url":"https:\/\/k12savings.com\/products\/oral-bioavailability-and-drug-delivery-isbn-9781119660651","provider":"K12savings","version":"1.0","type":"link"}