{"product_id":"drug-delivery-approaches-9781119772736","title":"Drug Delivery Approaches","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003ePreface xv\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Introduction: Utility of Mathematical Models in Drug Development and Delivery \u003c\/b\u003e\u003cb\u003e1\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eToufigh Gordi and Bret Berner\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction 1\u003c\/p\u003e \u003cp\u003e1.2 Use of Mathematical Models in Drug Development 2\u003c\/p\u003e \u003cp\u003e1.3 Noncompartmental Analysis 3\u003c\/p\u003e \u003cp\u003e1.4 Pharmacokinetic (PK) Models 5\u003c\/p\u003e \u003cp\u003e1.5 Physiologically Based Pharmacokinetic (PBPK) Models 7\u003c\/p\u003e \u003cp\u003e1.6 Pharmacokinetic\/Pharmacodynamic (PK\/PD) Models 9\u003c\/p\u003e \u003cp\u003e1.7 Systems Pharmacology Models 12\u003c\/p\u003e \u003cp\u003e1.8 Utility of PK\/PD Analysis and Models in Drug Development 14\u003c\/p\u003e \u003cp\u003e1.8.1 Drug Delivery and PK\/PD 26\u003c\/p\u003e \u003cp\u003e1.8.2 Drug Properties and Mechanism of Release from the Dosage Form 27\u003c\/p\u003e \u003cp\u003e1.8.2.1 Temporal Pattern of Delivery 30\u003c\/p\u003e \u003cp\u003e1.9 Discussion 32\u003c\/p\u003e \u003cp\u003eReferences 34\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Physiologically Based Models: Techniques and Applications to Drug Delivery \u003c\/b\u003e\u003cb\u003e43\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eRichard N. Upton, Ashley M. Hopkins, Ahmad Y. Abuhelwa, Jim H. Hughes and David J.R. Foster\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 43\u003c\/p\u003e \u003cp\u003e2.2 Types of Pharmacokinetic Models 43\u003c\/p\u003e \u003cp\u003e2.3 Commercial vs. Bespoke PBPK Models 45\u003c\/p\u003e \u003cp\u003e2.4 Data Sources 46\u003c\/p\u003e \u003cp\u003e2.5 Applications of PBPK Models 46\u003c\/p\u003e \u003cp\u003e2.6 Techniques of PBPK Modeling 48\u003c\/p\u003e \u003cp\u003e2.6.1 The “Language” of PBPK Models 48\u003c\/p\u003e \u003cp\u003e2.6.2 Oral Absorption Models 49\u003c\/p\u003e \u003cp\u003e2.6.3 Drug Metabolism and Drug–Drug Interactions 56\u003c\/p\u003e \u003cp\u003e2.6.4 Drug Transporters 58\u003c\/p\u003e \u003cp\u003e2.6.5 Renal Elimination 59\u003c\/p\u003e \u003cp\u003e2.6.6 Protein Binding 59\u003c\/p\u003e \u003cp\u003e2.6.7 Accounting for Size 61\u003c\/p\u003e \u003cp\u003e2.6.8 Accounting for Age 63\u003c\/p\u003e \u003cp\u003e2.6.9 Interspecies Scaling 64\u003c\/p\u003e \u003cp\u003e2.6.10 Between-Subject Variability 65\u003c\/p\u003e \u003cp\u003e2.6.11 Sensitivity Analysis 66\u003c\/p\u003e \u003cp\u003e2.6.12 Pharmacodynamics 66\u003c\/p\u003e \u003cp\u003e2.7 Summary 68\u003c\/p\u003e \u003cp\u003eReferences 68\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Oral Delivery and Pharmacokinetic Models \u003c\/b\u003e\u003cb\u003e75\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eWojciech Krzyzanski\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 75\u003c\/p\u003e \u003cp\u003e3.2 Compartmental Models 76\u003c\/p\u003e \u003cp\u003e3.2.1 First-Order Absorption 76\u003c\/p\u003e \u003cp\u003e3.2.2 Zero-Order Absorption 78\u003c\/p\u003e \u003cp\u003e3.2.3 Absorption Delay 78\u003c\/p\u003e \u003cp\u003e3.2.4 Parallel Inputs 80\u003c\/p\u003e \u003cp\u003e3.2.5 Discontinuous Absorption 81\u003c\/p\u003e \u003cp\u003e3.2.6 Compartmental Absorption and Transit 81\u003c\/p\u003e \u003cp\u003e3.2.7 Gastrointestinal Transit Time 82\u003c\/p\u003e \u003cp\u003e3.2.8 Other Compartmental Models 82\u003c\/p\u003e \u003cp\u003e3.3 Empirical Models 82\u003c\/p\u003e \u003cp\u003e3.3.1 Gamma Model 83\u003c\/p\u003e \u003cp\u003e3.3.2 Weibull Model 83\u003c\/p\u003e \u003cp\u003e3.3.3 Inverse Gaussian Model 85\u003c\/p\u003e \u003cp\u003e3.4 Physiologically Based Pharmacokinetic Models of Drug Absorption 85\u003c\/p\u003e \u003cp\u003e3.4.1 Traditional and Segregated-Flow Models 86\u003c\/p\u003e \u003cp\u003e3.5 Advanced PBPK Models 88\u003c\/p\u003e \u003cp\u003e3.5.1 Advanced Compartmental Absorption and Transit Model 88\u003c\/p\u003e \u003cp\u003e3.5.2 Advanced Dissolution Absorption and Metabolism Model 89\u003c\/p\u003e \u003cp\u003e3.6 Intestinal First-pass Drug Metabolism 90\u003c\/p\u003e \u003cp\u003e3.6.1 Well-stirred Gut Model 90\u003c\/p\u003e \u003cp\u003e3.6.2 \u003ci\u003eQ\u003c\/i\u003e\u003csub\u003eGut\u003c\/sub\u003e Model 91\u003c\/p\u003e \u003cp\u003e3.7 Spatiotemporal Models of Drug Absorption 91\u003c\/p\u003e \u003cp\u003e3.7.1 Dispersion Model 92\u003c\/p\u003e \u003cp\u003e3.7.2 Translocation Model 92\u003c\/p\u003e \u003cp\u003e3.8 Conclusions 93\u003c\/p\u003e \u003cp\u003eReferences 94\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Oral Site-Directed Drug Delivery and Influence on PK \u003c\/b\u003e\u003cb\u003e99\u003cbr\u003e\u003c\/b\u003e\u003ci\u003ePeter Scholes, Vanessa Zann, Wu Lin, Chris Roe and Bret Berner\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 99\u003c\/p\u003e \u003cp\u003e4.2 GI Anatomy and Physiology 99\u003c\/p\u003e \u003cp\u003e4.2.1 Anatomy 100\u003c\/p\u003e \u003cp\u003e4.2.2 Regional Variations in Physiology Affecting Drug Delivery 101\u003c\/p\u003e \u003cp\u003e4.2.2.1 Fluid Volume and pH 101\u003c\/p\u003e \u003cp\u003e4.2.2.2 Enzymes, GutWall Metabolism, Tissue Permeability, and Transporters 102\u003c\/p\u003e \u003cp\u003e4.2.2.3 Gender and Age Effects 111\u003c\/p\u003e \u003cp\u003e4.2.2.4 GI Transit 112\u003c\/p\u003e \u003cp\u003e4.2.2.5 Effect of Food 114\u003c\/p\u003e \u003cp\u003e4.2.2.6 Enterohepatic Circulation 115\u003c\/p\u003e \u003cp\u003e4.3 Biopharmaceutics Classification System (BCS) 116\u003c\/p\u003e \u003cp\u003e4.3.1 Background and Regulatory Perspectives 116\u003c\/p\u003e \u003cp\u003e4.3.2 Determining a Solubility Class 119\u003c\/p\u003e \u003cp\u003e4.3.3 Determining a Permeability Class 123\u003c\/p\u003e \u003cp\u003e4.3.4 Determining Dissolution of the Drug Product 125\u003c\/p\u003e \u003cp\u003e4.3.5 GI Stability 126\u003c\/p\u003e \u003cp\u003e4.3.6 Applications and Limitations of BCS Classification 126\u003c\/p\u003e \u003cp\u003e4.3.7 “Developability Classification System” 129\u003c\/p\u003e \u003cp\u003e4.4 Applications and Limitations of Characterization and Predictive Tools 131\u003c\/p\u003e \u003cp\u003e4.4.1 In Silico Tools: Predictive Models, Molecular Descriptors, and ADMET 131\u003c\/p\u003e \u003cp\u003e4.4.2 In Vitro Tools 133\u003c\/p\u003e \u003cp\u003e4.4.2.1 PAMPA 133\u003c\/p\u003e \u003cp\u003e4.4.2.2 Cell Lines 135\u003c\/p\u003e \u003cp\u003e4.4.3 Ex Vivo Tools 137\u003c\/p\u003e \u003cp\u003e4.4.3.1 Ussing Chambers 137\u003c\/p\u003e \u003cp\u003e4.4.3.2 Everted Intestinal Sac\/Ring 140\u003c\/p\u003e \u003cp\u003e4.4.4 In Situ Tools 142\u003c\/p\u003e \u003cp\u003e4.4.4.1 Closed Loop Intestinal Perfusion 143\u003c\/p\u003e \u003cp\u003e4.4.4.2 Single-Pass Intestinal Perfusion 143\u003c\/p\u003e \u003cp\u003e4.4.4.3 Intestinal Perfusion with Venous Sampling 143\u003c\/p\u003e \u003cp\u003e4.4.4.4 Vascularly Perfused Intestinal Models 144\u003c\/p\u003e \u003cp\u003e4.4.4.5 Other Animal Models 144\u003c\/p\u003e \u003cp\u003e4.4.5 In Vivo Tools 145\u003c\/p\u003e \u003cp\u003e4.4.6 In Silico Tools for Prediction of PK and PK\/PD 146\u003c\/p\u003e \u003cp\u003e4.4.7 Preclinical PK Models 150\u003c\/p\u003e \u003cp\u003e4.5 Tools to Probe Regional Bioavailability in Humans: Case Studies 151\u003c\/p\u003e \u003cp\u003e4.5.1 Site-Specific Delivery Devices 151\u003c\/p\u003e \u003cp\u003e4.5.2 Gamma Scintigraphic Imaging 157\u003c\/p\u003e \u003cp\u003e4.5.3 Magnetic Resonance Imaging (MRI) 159\u003c\/p\u003e \u003cp\u003e4.6 Rational Formulation Design and Effective Clinical Evaluation: Case Studies Describing How to Achieve Desired Release Modality and Target PK 160\u003c\/p\u003e \u003cp\u003e4.6.1 Formulation Strategies to Address BCS Classification Challenges 160\u003c\/p\u003e \u003cp\u003e4.6.1.1 Solubilization 160\u003c\/p\u003e \u003cp\u003e4.6.1.2 Permeability Enhancement 168\u003c\/p\u003e \u003cp\u003e4.6.1.3 Concluding Remarks on Strategies for BCS Challenges 170\u003c\/p\u003e \u003cp\u003e4.6.2 Formulation Strategies for Chronotherapeutic and Regional GI Delivery for Local or Systemic Delivery 170\u003c\/p\u003e \u003cp\u003e4.6.2.1 Gastric Retention 170\u003c\/p\u003e \u003cp\u003e4.6.2.2 Enteric-Coated Dosage Forms and Delayed Release to the Small Intestine 182\u003c\/p\u003e \u003cp\u003e4.6.2.3 Delivery to the Jejunum and Ileum 185\u003c\/p\u003e \u003cp\u003e4.6.2.4 Colonic Delivery 186\u003c\/p\u003e \u003cp\u003e4.7 Conclusions 191\u003c\/p\u003e \u003cp\u003eReferences 191\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 The Vasoconstrictor Assay (VCA): Then and Now \u003c\/b\u003e\u003cb\u003e221\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eIsadore Kanfer and Howard Maibach\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 221\u003c\/p\u003e \u003cp\u003e5.1.1 Applications and Procedures 222\u003c\/p\u003e \u003cp\u003e5.1.2 Visual Assessment 224\u003c\/p\u003e \u003cp\u003e5.1.3 Chromameter Assessment 225\u003c\/p\u003e \u003cp\u003e5.1.3.1 Comparison Between Visual and Chromameter Assessment 226\u003c\/p\u003e \u003cp\u003e5.2 Issues and Controversies 228\u003c\/p\u003e \u003cp\u003e5.2.1 Fitting of PD Response Data 228\u003c\/p\u003e \u003cp\u003e5.2.2 Circadian Activity 229\u003c\/p\u003e \u003cp\u003e5.2.3 BE Studies Performed Under Occlusion 230\u003c\/p\u003e \u003cp\u003e5.2.4 Erythema Response at Application Sites 230\u003c\/p\u003e \u003cp\u003e5.2.5 Use of VCA for Market Approval in the European Union 231\u003c\/p\u003e \u003cp\u003e5.2.6 Potency Ranking of Topical Corticosteroid Products 232\u003c\/p\u003e \u003cp\u003e5.2.7 Sensitive Region of the Dose–Response Curve 234\u003c\/p\u003e \u003cp\u003e5.2.8 Correlation of ED\u003csub\u003e50\u003c\/sub\u003e with Potency Classification of a Product? 235\u003c\/p\u003e \u003cp\u003e5.3 Conclusions 236\u003c\/p\u003e \u003cp\u003eReferences 236\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Topical Delivery: Toward an IVIVC \u003c\/b\u003e\u003cb\u003e241\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSam G. Raney and Thomas J. Franz\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 241\u003c\/p\u003e \u003cp\u003e6.2 In Vitro–In Vivo Correlation: Validating the Model of Topical Delivery 241\u003c\/p\u003e \u003cp\u003e6.3 In Vitro–In Vivo Correlation: Transdermal Delivery 244\u003c\/p\u003e \u003cp\u003e6.4 In Vitro–In Vivo Correlation: Bioavailability and Bioequivalence 245\u003c\/p\u003e \u003cp\u003e6.5 Summary 250\u003c\/p\u003e \u003cp\u003eDisclaimer 250\u003c\/p\u003e \u003cp\u003eReferences 250\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Integrated Transdermal Drug Delivery and Pharmacokinetics in Development \u003c\/b\u003e\u003cb\u003e253\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eBret Berner and Gregory M. Kochak\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 253\u003c\/p\u003e \u003cp\u003e7.2 Fundamentals of Transdermal Delivery 254\u003c\/p\u003e \u003cp\u003e7.2.1 Architecture of Skin 254\u003c\/p\u003e \u003cp\u003e7.2.2 Skin Permeation and Transdermal Delivery 255\u003c\/p\u003e \u003cp\u003e7.2.3 Basic Pharmacokinetics of Transdermal Delivery 262\u003c\/p\u003e \u003cp\u003e7.3 In Vivo Assessment of Drug Input and Pharmacokinetic Disposition 266\u003c\/p\u003e \u003cp\u003e7.3.1 Deconvolution 266\u003c\/p\u003e \u003cp\u003e7.3.2 Convolution 267\u003c\/p\u003e \u003cp\u003e7.3.3 Instability in Deconvolution 269\u003c\/p\u003e \u003cp\u003e7.3.4 Generalized Input and Convolution 272\u003c\/p\u003e \u003cp\u003e7.4 In Vitro Testing: Drug Release from Transdermal Systems 273\u003c\/p\u003e \u003cp\u003e7.5 In Vitro\/In Vivo Correlation 275\u003c\/p\u003e \u003cp\u003e7.6 Clinical Safety and Efficacy Studies for Dermal Drug Development 280\u003c\/p\u003e \u003cp\u003e7.6.1 Bioavailability and Bioequivalence 281\u003c\/p\u003e \u003cp\u003e7.6.2 Skin Irritation and Sensitization Study 282\u003c\/p\u003e \u003cp\u003e7.7 Dosage Form Proportionality Scaling and Dose Proportionality 283\u003c\/p\u003e \u003cp\u003e7.7.1 Residual Content of the Dosage Form 283\u003c\/p\u003e \u003cp\u003e7.7.2 Comparative Toxicity and Efficacy 283\u003c\/p\u003e \u003cp\u003e7.8 Supporting In Vitro Studies 283\u003c\/p\u003e \u003cp\u003e7.9 Safety Studies Related to Environmental Conditions Such as Heat and Storage Conditions 284\u003c\/p\u003e \u003cp\u003e7.10 Active Transdermal Systems That Enhance Barrier Penetration 284\u003c\/p\u003e \u003cp\u003e7.10.1 Microneedles 284\u003c\/p\u003e \u003cp\u003e7.10.2 Thermal or Radio Frequency Ablation 287\u003c\/p\u003e \u003cp\u003e7.10.3 Sonophoresis 288\u003c\/p\u003e \u003cp\u003e7.10.4 Electrical 289\u003c\/p\u003e \u003cp\u003e7.10.4.1 Electroporation 289\u003c\/p\u003e \u003cp\u003e7.10.4.2 Iontophoresis 290\u003c\/p\u003e \u003cp\u003e7.11 Conclusion 293\u003c\/p\u003e \u003cp\u003eReferences 293\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Formulation and Pharmacokinetic Challenges Associated with Targeted Pulmonary Drug Delivery \u003c\/b\u003e\u003cb\u003e305\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eTomoyuki Okuda and Hak-Kim Chan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Progress on Formulations and Devices for Inhaled Drugs 305\u003c\/p\u003e \u003cp\u003e8.2 Challenges for Inhaled Formulations 308\u003c\/p\u003e \u003cp\u003e8.2.1 High-Dose Drugs and Amorphous Powders 308\u003c\/p\u003e \u003cp\u003e8.2.2 Generic DPI Formulations 309\u003c\/p\u003e \u003cp\u003e8.2.3 Biologics and Macromolecules 310\u003c\/p\u003e \u003cp\u003e8.2.4 Controlled Release Formulations 310\u003c\/p\u003e \u003cp\u003e8.3 Factors Determining the Fate of Inhaled Drugs in the Body 311\u003c\/p\u003e \u003cp\u003e8.3.1 Anatomical and Histological Characteristics of the Respiratory System 311\u003c\/p\u003e \u003cp\u003e8.3.2 Physicochemical Characteristics of Inhaled Drugs 312\u003c\/p\u003e \u003cp\u003e8.4 Pharmacokinetic\/Pharmacodynamic Correlation of Inhaled Drugs 314\u003c\/p\u003e \u003cp\u003e8.4.1 Desirable Pharmacokinetic Parameters of Inhaled Drugs for Local Action and Systemic Delivery 314\u003c\/p\u003e \u003cp\u003e8.4.2 Pharmacokinetic\/Pharmacodynamic Correlation of Clinically Approved Inhaled Drugs 315\u003c\/p\u003e \u003cp\u003e8.4.2.1 Corticosteroids and Bronchodilators 315\u003c\/p\u003e \u003cp\u003e8.4.2.2 Antimicrobials 316\u003c\/p\u003e \u003cp\u003e8.4.2.3 Prostacyclin Analogs 317\u003c\/p\u003e \u003cp\u003e8.4.2.4 Loxapine 318\u003c\/p\u003e \u003cp\u003e8.4.2.5 Insulin 318\u003c\/p\u003e \u003cp\u003e8.5 Application of Drug Delivery System for Improving Pharmacokinetic\/Pharmacodynamic Parameters of Inhaled Drugs 320\u003c\/p\u003e \u003cp\u003e8.5.1 Chemical Modification 320\u003c\/p\u003e \u003cp\u003e8.5.2 Functional Micro\/Nanoparticle Formulations 321\u003c\/p\u003e \u003cp\u003e8.5.3 Active Targeting 322\u003c\/p\u003e \u003cp\u003e8.6 Conclusion 323\u003c\/p\u003e \u003cp\u003eReferences 324\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Oral Transmucosal Drug Delivery \u003c\/b\u003e\u003cb\u003e333\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMohammed Sattar and Majella E. Lane\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 333\u003c\/p\u003e \u003cp\u003e9.2 Structure and Physiology of the Oral Mucosa 334\u003c\/p\u003e \u003cp\u003e9.2.1 Buccal Mucosa 334\u003c\/p\u003e \u003cp\u003e9.2.2 Sublingual Mucosa 335\u003c\/p\u003e \u003cp\u003e9.2.3 Gingiva and Palate 336\u003c\/p\u003e \u003cp\u003e9.2.4 Saliva 336\u003c\/p\u003e \u003cp\u003e9.2.5 Mucus 336\u003c\/p\u003e \u003cp\u003e9.2.6 Permeation Routes 336\u003c\/p\u003e \u003cp\u003e9.3 Drug Properties Which Influence OTMD 337\u003c\/p\u003e \u003cp\u003e9.3.1 Molecular Weight 337\u003c\/p\u003e \u003cp\u003e9.3.2 Lipid Solubility 338\u003c\/p\u003e \u003cp\u003e9.3.3 Degree of Ionization 339\u003c\/p\u003e \u003cp\u003e9.3.4 Potency 340\u003c\/p\u003e \u003cp\u003e9.4 Buccal and Sublingual Formulations 340\u003c\/p\u003e \u003cp\u003e9.4.1 Currently Used Technologies 340\u003c\/p\u003e \u003cp\u003e9.4.2 Investigation of Iontophoresis for Oral Transmucosal Drug Delivery 342\u003c\/p\u003e \u003cp\u003e9.5 Models to Study OTDD 342\u003c\/p\u003e \u003cp\u003e9.5.1 Studies in Man and Human Tissue Models 342\u003c\/p\u003e \u003cp\u003e9.5.2 Porcine Tissue Models 343\u003c\/p\u003e \u003cp\u003e9.5.3 Dog, Monkey, and Rabbit Models 344\u003c\/p\u003e \u003cp\u003e9.5.4 Chicken, Hamster, and Rat Models 345\u003c\/p\u003e \u003cp\u003e9.5.5 Cell Culture Models 345\u003c\/p\u003e \u003cp\u003e9.6 Feasibility of Systemic Delivery Based on In Vitro Permeation Studies 346\u003c\/p\u003e \u003cp\u003e9.7 Conclusion 347\u003c\/p\u003e \u003cp\u003eReferences 347\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 PK\/PD and the Drug Delivery Regimen for Infusion in the Critical Care Setting \u003c\/b\u003e\u003cb\u003e355\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eFekade B. Sime and Jason A. Roberts\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 355\u003c\/p\u003e \u003cp\u003e10.2 PK\/PD Properties and the Mode of Infusional Drug Delivery for Antibiotics 356\u003c\/p\u003e \u003cp\u003e10.3 Changes in PK\u003ci\u003e\/\u003c\/i\u003ePD and Infusional Drug Delivery Regimens in Critically Ill Patients 357\u003c\/p\u003e \u003cp\u003e10.4 Short Intermittent Infusions 359\u003c\/p\u003e \u003cp\u003e10.5 Extended Infusions 360\u003c\/p\u003e \u003cp\u003e10.6 Continuous Infusion 361\u003c\/p\u003e \u003cp\u003e10.6.1 Continuous Infusion of β-Lactam Antibiotics 361\u003c\/p\u003e \u003cp\u003e10.6.2 Continuous Infusion of Vancomycin 366\u003c\/p\u003e \u003cp\u003e10.7 Conclusions 367\u003c\/p\u003e \u003cp\u003eReferences 367\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Virtual Experiment Methods for Integrating Pharmacokinetic, Pharmacodynamic, and Drug Delivery Mechanisms: Demonstrating Feasibility for Acetaminophen Hepatotoxicity \u003c\/b\u003e\u003cb\u003e375\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eAndrew K. Smith, Ryan C. Kennedy, Brenden K. Petersen, Glen E.P. Ropella and Carver Anthony Hunt\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 375\u003c\/p\u003e \u003cp\u003e11.1.1 Focus on Acetaminophen-Induced Liver Injury 376\u003c\/p\u003e \u003cp\u003e11.2 Results 377\u003c\/p\u003e \u003cp\u003e11.2.1 Engineering Parsimonious Fit for Purpose Virtual Mice 377\u003c\/p\u003e \u003cp\u003e11.2.2 Concrete Lobule Location-Dependent Mechanisms 380\u003c\/p\u003e \u003cp\u003e11.2.3 Falsifying Virtual Mechanisms 381\u003c\/p\u003e \u003cp\u003e11.2.4 A Plausible Causal Cascade 383\u003c\/p\u003e \u003cp\u003e11.2.5 Drug Delivery and a Therapeutic Intervention 385\u003c\/p\u003e \u003cp\u003e11.3 Methods 386\u003c\/p\u003e \u003cp\u003e11.3.1 Broad Requirements 386\u003c\/p\u003e \u003cp\u003e11.3.2 Prediction 388\u003c\/p\u003e \u003cp\u003e11.3.3 Iterative Refinement Protocol 388\u003c\/p\u003e \u003cp\u003e11.3.4 Data Types, Reuse, and Sharing 390\u003c\/p\u003e \u003cp\u003e11.3.5 Quality Assurance and Control 390\u003c\/p\u003e \u003cp\u003e11.3.6 Building Mouse Analog Credibility 391\u003c\/p\u003e \u003cp\u003e11.3.6.1 Validation 391\u003c\/p\u003e \u003cp\u003e11.3.6.2 Verification 392\u003c\/p\u003e \u003cp\u003e11.3.7 Liver and Lobular Form and Function 392\u003c\/p\u003e \u003cp\u003e11.3.8 APAP Metabolism 393\u003c\/p\u003e \u003cp\u003e11.3.9 PP-to-CV Gradients 394\u003c\/p\u003e \u003cp\u003e11.3.10 GSH Depletion 394\u003c\/p\u003e \u003cp\u003e11.3.11 Damage Products 395\u003c\/p\u003e \u003cp\u003e11.3.12 Triggering Hepatocyte Death 395\u003c\/p\u003e \u003cp\u003e11.3.13 Repair Events 395\u003c\/p\u003e \u003cp\u003e11.3.14 Sensitivity Analyses and Uncertainty Quantification 396\u003c\/p\u003e \u003cp\u003e11.3.15 Mouse Body 397\u003c\/p\u003e \u003cp\u003e11.3.16 Death Delay 399\u003c\/p\u003e \u003cp\u003e11.4 Discussion 399\u003c\/p\u003e \u003cp\u003eReferences 402\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Personalized Medicine: Drug Delivery and Pharmacokinetics \u003c\/b\u003e\u003cb\u003e407\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eMelanie A. Felmlee and Xiaoling Li\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Personalized Medicine 407\u003c\/p\u003e \u003cp\u003e12.2 Drug Delivery in Personalized Medicine 409\u003c\/p\u003e \u003cp\u003e12.2.1 Delivery Approaches to Alter Dose 410\u003c\/p\u003e \u003cp\u003e12.2.2 Delivery Approaches That Alter Pharmacokinetic Parameters 412\u003c\/p\u003e \u003cp\u003e12.2.3 Targeted Delivery Approaches 413\u003c\/p\u003e \u003cp\u003e12.3 Pharmacokinetic Analysis for Personalized Drug Delivery 414\u003c\/p\u003e \u003cp\u003e12.3.1 Pharmacokinetic Analysis for Non-targeted Delivery Approaches 414\u003c\/p\u003e \u003cp\u003e12.3.2 Pharmacokinetic Analysis for Targeted Delivery Approaches 416\u003c\/p\u003e \u003cp\u003e12.4 Challenges and Opportunities in Personalized Drug Delivery 417\u003c\/p\u003e \u003cp\u003e12.5 Conclusions 418\u003c\/p\u003e \u003cp\u003eReferences 419\u003c\/p\u003e \u003cp\u003eIndex 423\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49407147508055,"sku":"9781119772736","price":169.16,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119772736.jpg?v=1730498335","url":"https:\/\/bookcurl.com\/products\/drug-delivery-approaches-9781119772736","provider":"Book Curl","version":"1.0","type":"link"}