List of Contributors xxix Foreword xxxix Preface xli 1 Barriers to Oral Bioavailability - An Overview 1 Ming Hu and Xiaoling li 1.1 Introduction 1 References 4 2 Solubility of Pharmaceutical Solids 5 Pramila Sharma, Yi Gao, Heran li, Bhaskara R. Jasti, Sanming li, and Xiaoling li 2.1 Introduction 5 2.2 Fundamentals of Solubility 6 2.3 Solubility and Oral Bioavailability 19 2.4 Strategies to Improve Solubility 21 2.5 Summary 24 Abbreviations 25 References 25 3 In Vitro Dissolution of Pharmaceutical Solids 31 Tze Ning Hiew and Paul W.
S. Heng 3.1 Dissolution Theory and Fundamentals 31 3.2 Dissolution of Drug Products 34 3.3 In Vitro Dissolution Methods for Ensuring Quality of Commercial Drug Products 36 3.4 In Vitro Dissolution Methods in Product Development 38 3.5 Automation in Dissolution Testing and Prediction 40 3.6 Conclusions 42 References 42 4 Biological and Physiological Features of the Gastrointestinal Tract Relevant to Oral Drug Absorption 47 Paul C.
L. Ho 4.1 Introduction 47 4.2 Biological Features of Gastrointestinal Tract 47 4.3 Physiological Features of Gastrointestinal Tract 51 4.4 Other Physiological Factors 54 4.5 Conclusion 56 References 56 5 Absorption of Drugs Via Passive Diffusion and Carrier-Mediated Pathways 61 Amit Kokate, Jae H. Chang, and Miki S.
Park Disclaimer 61 5.1 Introduction 61 5.2 Passive Diffusion 62 5.3 Carrier-Mediated Transport 67 5.4 Summary 75 References 75 6 Determinant Factors for Passive Absorption of Drugs 79 Wei Zhu and Mikolaj Milewski 6.1 Introduction 79 6.2 Fundamentals of Drug Absorption 79 6.3 Absorption Determining Factors 82 6.
4 Rate Limiting Steps in Absorption and Prediction of Dosing Amount Absorbed 86 6.5 Overview of In Silico Prediction of Absorption and Pharmacokinetics for Oral Dosage Forms 88 6.6 Summary 89 References 90 7 Protein Binding and Drug Distribution 95 HaiAn Zheng and Marcel Musteata 7.1 Introduction 95 7.2 Protein-Drug Binding in Plasma 95 7.3 Modeling of Binding Equilibria 97 7.4 Bioanalytical Methods for Studying Drug-Protein Binding 98 7.5 Impact of Drug-Protein Binding on Pharmacokinetic Parameters 105 7.
6 Physicochemical Factors that Affect Protein-Drug Binding and Drug Distribution 106 7.7 Physiological and Pathological Factors that Affect Protein-Drug Binding and Drug Distribution 107 References 107 8 Drug Transport Across the Placental Barrier 111 Valentina Bryant, Mansi Shah, Jennifer Waltz, and Erik Rytting 8.1 Introduction 111 8.2 Pharmacokinetics of Drugs Administered During Pregnancy 111 8.3 Placental Development and Structure 112 8.4 Functions of the Human Placenta 113 8.5 Mechanisms of Drug Transport Across the Placenta 114 8.6 Mechanisms of Drug Metabolism Within the Placenta 116 8.
7 Strategies to Alter Drug Transport Across the Placenta 117 8.8 Experimental Models of the Human Placenta 118 References 122 9 Biopharmaceutics Classification System: Theory and Practice 131 Mehul Mehta, Jayabharathi Vaidyanathan, and Lawrence Yu 9.1 Introduction 131 9.2 Theory 131 9.3 BCS-based Biowaiver 134 9.4 BCS Waiver Case Studies 136 9.5 BCS: Additional Regulatory Applications 138 9.6 Summary 138 References 139 10 Effects of Food on Drug Absorption 141 Zhu Zhou, Venugopal P.
Marasanapalle, Xiaoling Li, and Bhaskara R. Jasti 10.1 Introduction 141 10.2 Mechanisms of Food Effects 147 10.3 Prediction of Food Effects 149 10.4 Summary 149 Abbreviations 150 References 150 11 Drug Metabolism in Gastrointestinal Tract 155 Rashim Singh, Dinh Bui, and Ming Hu 11.1 Introduction 155 11.2 Role of Intestinal Efflux Transporters in the Drug Disposition 161 11.
3 Drug Metabolism-Transporter Coupling in Drug Disposition in GIT 163 11.4 Factors Affecting Intestinal Drug Metabolism 168 11.5 Biopharmaceutics Drug Disposition Classification System 170 11.6 Metabolism-Based Drug-Drug and Drug-Natural Product Interactions 171 11.7 Metabolic Interactions Between Gut Microbiome and Drugs in GIT 173 11.8 Metabolism-Based Xenobiotic-Induced Toxicity 174 11.9 GIT Metabolism-Based Drug-Designing and Lead Optimization in Drug Development 174 11.10 Summary 175 Abbreviations 176 References 176 12 Liver Drug Metabolism 189 Ritika Kurian, Leslie T.
Steen, and Hongbing Wang 12.1 Introduction 189 12.2 Hepatic Structure and Function 189 12.3 Phase I Drug Metabolism 191 12.4 Phase II Drug Metabolism 199 12.5 Novel Platforms for Drug Metabolism Studies 204 12.6 Drug Metabolism and Its Impact on Adverse Drug Reactions 205 12.7 Conclusion 207 References 207 13 Urinary Excretion of Drugs and Drug Reabsorption 213 Jessica T.
Babic, Jack Cook, and Vincent H. Tam 13.1 Introduction 213 13.2 Kidney as an Eliminating Organ 213 13.3 Drug Transporters and Their Role in Renal Elimination 220 13.4 Renal Elimination and Bioavailability 222 13.5 Augmented Renal Clearance 227 References 228 14 Excretion of Drugs and Their Metabolites into the Bile 233 Song Gao, Imoh Etim, Robin Sunsong, Christabel Ebuzoeme, Ting Du, and Dinh Bui 14.1 Introduction 233 14.
2 Anatomy and Physiology of the Liver and Biliary System 234 14.3 Biliary Excreted Drugs and Metabolites 235 14.4 Impact of Biliary Excretion on ADME and Pharmacokinetics 235 14.5 Hepatic Transporters Involved in Biliary Excretion 245 14.6 Factors Affecting Biliary Secretion 248 14.7 Biliary Excretion Research Models 250 14.8 Concluding Remarks 255 Abbreviations 255 References 255 15 Pharmacokinetic Behaviors of Orally Administered Drugs 267 Hamdah Al Nebaihi, Dion R. Brocks, Jaime A.
Yáñez, Marcus Laird Forrest, and Neal M. Davies Objectives 267 15.1 Introduction 267 15.2 Physicochemical Factors Affecting Oral Concentration Time Profiles 274 15.3 Physiological Factors Affecting Oral Concentration Time Profiles 281 15.4 Food-Effects and Oral Concentration Time Profiles 296 15.5 The Impact of the Lymphatic System on Oral Bioavailability 298 15.6 Summation 303 Abbreviations 304 References 304 16 In Vitro-In Vivo Correlations of Pharmaceutical Dosage Forms 315 Deliang Zhou and Yihong Qiu 16.
1 Introduction 315 16.2 Categories of In Vitro-In Vivo Correlations 316 16.3 Convolution and Deconvolution 317 16.4 Development and Assessments of an IVIVC 321 16.5 Applications of an IVIVC 324 16.6 Challenges 325 16.7 Physiologically Based Biopharmaceutics Models (PBBM) 326 16.8 Summary 328 References 329 17 Advanced Concepts in Oral Bioavailability Research - An Overview 333 Baojian Wu, Min Chen, and Ming Hu Abbreviations 336 References 336 18 Expression and Pharmaceutical Relevance of Intestinal Transporters 339 Melanie A.
Felmlee, Michael Ng, and Annie Lee 18.1 Introduction 339 18.2 Intestinal Drug Transport 340 18.3 Uptake Transporters 341 18.4 Efflux Transporters 350 18.5 Summary 353 References 353 19 Amino Acid Transporters 361 Liping Wang, Xiaoyan Li, Mengdi Ying, Ming Hu, and Zhongqiu Liu 19.1 Introduction 361 19.2 Classification of Amino Acid Transporters and their Functions 364 19.
3 Epithelial Amino Acid Transporters 372 19.4 Endothelial Amino Acid Transporters 378 19.5 Regulation of Amino Acid Transport 380 19.6 Conclusion 382 Abbreviations 382 References 383 20 Drug Transporters and Their Role in Absorption and Disposition of Peptides and Peptide-Based Pharmaceuticals 393 David 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 20.1 Introduction 393 20.2 Transport Systems Mediating Peptide-based Pharmaceutical Absorption and Disposition: The Solute Carrier (SLC) Family 397 20.3 ATP Binding Cassette (ABC) Transporters 399 20.4 Gastrointestinal Tract-Specific Transporter Activity 400 20.
5 Conclusions 407 Acknowledgments 408 References 408 21 OATP Transporters in Hepatic and Intestinal Uptake of Orally Administered Drugs 417 Wei Yue, Taleah Farasyn, Alexandra Crowe, Khondoker Alam, Lucila Garcia-Contreras, Yifan Tu, and Lu Wang 21.1 Introduction 417 21.2 Hepatic OATP1B1 and OATP1B 3 417 21.3 OATP2B1 in the Intestine 420 21.4 OATP1A2 in the intestine 421 21.5 Summary 422 Acknowledgement 422 References 422 22 ABC Transporters in Intestinal and Liver Efflux 429 Marilyn E. Morris and Tianjing Ren 22.1 Introduction 429 22.
2 Apical Membrane Efflux Proteins 430 22.3 Basolateral/Lateral Membrane Efflux Proteins 442 22.4 Clinical Relevance of ABC Transporters in Oral Bioavailability of Drugs 444 22.5.