| Contents |
Cover -- Title Page -- Copyright Page -- Contents -- Preface -- Chapter 1 Setting the Scene: Concepts, Nature of Drugs, and Quality of Results -- 1.1 Introduction -- 1.2 Concepts and terminology: disposition and pharmacokinetics -- 1.3 Pharmacokinetic parameters -- 1.3.1 Half-life -- 1.3.2 Clearance and apparent volume of distribution -- 1.3.3 Area under the plasma concentration-time curve -- 1.3.4 Apparent oral clearance -- 1.4 Time-concentration-effect relationships -- 1.5 Properties of drugs and xenobiotics -- 1.6 Quality of the data -- 1.6.1 Quantification of analyte concentrations -- 1.6.2 Timing of samples -- 1.6.3 Quality control and method validation -- 1.7 References -- Chapter 2 Drug Disposition and Fate -- 2.1 Introduction -- 2.2 Transport proteins -- 2.3 Absorption -- 2.3.1 Gastrointestinal tract -- 2.3.2 Drug transfer across the gastrointestinal tract -- 2.3.3 Other mucus membranes -- 2.3.4 Skeletal muscle -- 2.3.5 Skin -- 2.3.6 Absorption of macromolecules and nanoparticles -- 2.4 Distribution -- 2.4.1 Mechanisms of sequestration -- 2.4.2 Assessing the extent and location of distribution -- 2.4.3 Kinetics of distribution -- 2.5 Metabolism -- 2.5.1 Phase 1 metabolism -- 2.5.2 Phase 2 conjugations -- 2.5.3 Metabolism by microbiota -- 2.6 Excretion -- 2.6.1 Urine -- 2.6.2 Biliary excretion -- 2.6.3 Expired air -- 2.6.4 Saliva -- 2.6.5 Stomach and intestine -- 2.6.6 Breast milk -- 2.6.7 Other routes of excretion -- 2.6.8 Cycling processes -- 2.7 References -- Chapter 3 Pharmacokinetic Modelling -- 3.1 Introduction -- 3.2 Fundamental concepts -- 3.2.1 Apparent volume of distribution -- 3.2.2 Clearance -- 3.3 Elimination -- 3.3.1 First-order elimination -- 3.3.2 Non-linear elimination -- 3.4 Intravenous infusions -- 3.4.1 Single-compartment model with first-order elimination -- 3.4.2 Two-compartment model with first-order elimination. |
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3.5 First-order input and elimination -- 3.5.1 Absorption -- 3.5.2 Multiple dosing -- 3.6 Areas under the plasma concentration-time curve: trapezoidal method -- 3.7 Statistical moment theory -- 3.7.1 Estimating AUMC -- 3.8 Bioavailability and bioequivalence -- 3.8.1 Non-linear kinetics -- 3.8.2 Effect of systemic availability on plasma concentration-time curves -- 3.8.3 Factors affecting bioavailability -- 3.8.4 Bioequivalence -- 3.9 Physiological modelling -- 3.9.1 Practical considerations -- 3.10 Population kinetics -- 3.11 References -- Chapter 4 Pharmacokinetics of Metabolism and Excretion -- 4.1 Introduction -- 4.2 Metabolite kinetics -- 4.2.1 Basic concepts -- 4.2.2 Fraction of metabolite formed -- 4.2.3 More complex situations -- 4.2.4 Effect of pre-systemic metabolism -- 4.2.5 Interconversion of drug and metabolite -- 4.2.6 Active metabolites and prodrugs -- 4.2.7 Kinetics of formed and preformed metabolites -- 4.3 Kinetics of urinary excretion -- 4.3.1 Renal clearance -- 4.3.2 Effect of urine flow rate -- 4.3.3 Estimating renal blood flow and glomerular filtration rate -- 4.3.4 Specific drug examples -- 4.4 Excretion in faeces -- 4.5 References -- Chapter 5 Quantitative Pharmacological Relationships -- 5.1 Introduction -- 5.2 Concentration-effect relationships and dose-response curves -- 5.3 Concentration-effect relationships in vivo -- 5.4 Time-Dependent Models -- 5.4.1 Direct link and indirect link models -- 5.4.2 Temporal displacement -- 5.4.3 Inhomogeneity of plasma -- 5.4.4 Effects of unequal distribution in plasma -- 5.4.5 Pharmacokinetic distributional models -- 5.5 PK-PD modelling -- 5.5.1 PK-PD modelling under steady-state conditions -- 5.5.2 Use of effect-compartment models -- 5.5.3 Indirect-response models -- 5.5.4 Disease progression models -- 5.5.5 Time-related changes in pharmacodynamic parameters -- 5.5.6 Schedule dependence. |
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5.5.7 Basic PK-PD versus system PK-PD -- 5.6 References -- Chapter 6 Predictive Pharmacokinetics -- 6.1 Introduction -- 6.2 Physiochemical properties -- 6.2.1 Druggability -- 6.2.2 Drug-likeness -- 6.2.3 Dissolution studies -- 6.3 Metabolic stability -- 6.3.1 Microsomal intrinsic clearance -- 6.3.2 Hepatocytes -- 6.3.3 Recombinant human cytochromes -- 6.4 Plasma protein and tissue binding and blood/plasma ratios -- 6.4.1 Plasma protein binding -- 6.4.2 Erythrocyte concentrations -- 6.5 Hepatic clearance -- 6.5.1 Hepatic intrinsic clearance -- 6.5.2 Effect of plasma protein binding on elimination kinetics -- 6.6 Experimental methods of assessing transfer across biological membranes -- 6.6.1 Cell culture -- 6.6.2 Parallel artificial membrane permeability assay -- 6.6.3 Ussing chambers -- 6.6.4 Intestinal sacs -- 6.6.5 In vivo/in situ studies -- 6.7 Allometric scaling -- 6.7.1 Refinements to allometric scaling -- 6.7.2 Practical aspects of allometry -- 6.7.3 Method of Wajima -- 6.8 In silico predictions and PBPK modelling -- 6.9 Microdosing studies -- 6.10 Translational science -- 6.11 References -- Chapter 7 Disposition of Peptides and Other Biological Molecules -- 7.1 Introduction -- 7.2 Chemical aspects -- 7.2.1 PEGylation -- 7.3 Assay methods -- 7.4 Pharmacokinetics -- 7.4.1 Administration and dosage -- 7.4.2 Bioequivalence and biosimilarity -- 7.4.3 Distribution -- 7.4.4 Metabolism -- 7.4.5 Excretion -- 7.5 Plasma kinetics and pharmacodynamics -- 7.6 Examples of particular interest -- 7.6.1 Botulinum toxins -- 7.6.2 Cholecystokinins -- 7.6.3 Ciclosporin -- 7.6.4 Cocaine hydrolases -- 7.6.5 Erythropoietin -- 7.6.6 Heparin -- 7.6.7 Mipomersen -- 7.6.8 Somatotropin -- 7.6.9 Vasopressin and desmopressin -- 7.7 References -- Chapter 8 Monoclonal Antibodies -- 8.1 Introduction -- 8.2 Nomenclature -- 8.3 Circulation of monoclonal antibodies. |
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8.3.1 Convection -- 8.3.2 Neonatal Fc receptor -- 8.3.3 Binding to soluble target antigens -- 8.4 Pharmaceutical and DMPK aspects -- 8.4.1 Routes of administration -- 8.4.2 Distribution and apparent volume of distribution -- 8.4.3 Metabolism and excretion -- 8.4.4 Pharmacokinetics -- 8.4.5 Individual and population pharmacokinetics -- 8.5 Development of orally administered monoclonal antibodies -- 8.6 Optimizing pharmacokinetic and pharmacodynamic properties -- 8.7 Two highlighted early and durable examples -- 8.7.1 Trastuzumab -- 8.7.2 Adalimumab -- 8.8 PBPK modelling -- 8.9 Antibody-drug conjugates -- 8.9.1 Payloads -- 8.9.2 Linkers -- 8.9.3 Bystander killing -- 8.9.4 Disposition and pharmacokinetics -- 8.10 References -- Chapter 9 Drug Metabolism and Pharmacokinetics in Veterinary Sciences -- 9.1 Introduction -- 9.2 Areas of practice -- 9.2.1 Companion animal medicine -- 9.2.2 Treatment of animals of commerce -- 9.2.3 Zoos and wildlife preserves -- 9.2.4 Laboratory animal medicine -- 9.3 Scientific approach including allometric scaling -- 9.4 Information organized by pharmacokinetic processes -- 9.4.1 Administration -- 9.4.2 Absorption -- 9.4.3 Tissue distribution -- 9.4.4 Plasma protein binding and transporters -- 9.4.5 Metabolism -- 9.4.6 Excretion -- 9.5 Information organized by species and drugs -- 9.5.1 Mammals -- 9.5.2 Fish -- 9.6 Some drugs unique to veterinary science -- 9.7 Accidental exposure: toxicology - drugs used by humans that are dangerous to animals -- 9.7.1 Paracetamol in cats -- 9.7.2 Xanthines: chocolate in dogs -- 9.8 Residue analysis -- 9.9 References -- Chapter 10 Factors Affecting Plasma Concentrations: Consideration of Special Populations -- 10.1 Introduction -- 10.2 Pharmaceutical factors -- 10.3 Weight and obesity -- 10.3.1 Effects of obesity on pharmacokinetics -- 10.3.2 Dose adjustment in obesity. |
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10.3.3 Oral contraceptives -- 10.3.4 Gastric bypass surgery -- 10.3.5 Psychiatric patients -- 10.4 Food, diet, and nutrition -- 10.4.1 Diet and nutrition -- 10.5 Time of day -- 10.5.1 Circadian rhythms -- 10.5.2 Absorption -- 10.5.3 The liver -- 10.5.4 The kidneys -- 10.5.5 Intravenous and other injected doses -- 10.5.6 Pharmacodynamics -- 10.6 Posture and exercise -- 10.6.1 Exercise -- 10.7 Smoking -- 10.8 References -- Chapter 11 Pharmacogenetics, Pharmacogenomics, and Precision Medicine -- 11.1 Introduction -- 11.1.1 Terminology -- 11.2 Methods for the study of pharmacogenetics -- 11.2.1 Studies in twins -- 11.2.2 Phenotyping and genotyping -- 11.3 N-Acetyltransferase -- 11.3.1 Isoniazid -- 11.3.2 Sulfonamides -- 11.3.3 Other drugs -- 11.3.4 Genotyping N-acetyltransferase -- 11.4 Plasma cholinesterase -- 11.4.1 Suxamethonium -- 11.5 Carboxylesterases -- 11.6 Cytochrome P450 polymorphisms -- 11.6.1 Cytochrome 2D6 -- 11.6.2 Cytochrome 2C9 -- 11.6.3 Cytochrome 2C19 -- 11.6.4 Cytochromes 3A4/5 -- 11.6.5 Other cytochrome P450 polymorphisms -- 11.7 Glucose-6-phosphate dehydrogenase -- 11.7.1 Glucose-6-phosphate dehydrogenase deficiency -- 11.7.2 Triggering -- 11.7.3 Effects on pharmacokinetics -- 11.8 Alcohol dehydrogenase and acetaldehyde dehydrogenase -- 11.9 Thiopurine methyltransferase -- 11.10 Phase 2 enzymes -- 11.10.1 UDP-glucuronosyltransferases -- 11.10.2 Sulfotransferases -- 11.10.3 Glutathione transferases -- 11.11 Transporters -- 11.12 Pharmacodynamic differences -- 11.13 Ethnicity -- 11.14 Personalized medicine -- 11.15 References -- Chapter 12 Effects of Sex and Pregnancy on Drug Disposition and Pharmacokinetics -- 12.1 Introduction -- 12.1.1 Studies in animals -- 12.2 Effect of sex on human drug disposition and pharmacokinetics -- 12.2.1 Absorption and bioavailability -- 12.2.2 Distribution -- 12.2.3 Metabolism -- 12.2.4 Excretion. |
| Abstract |
"An authoritative, comprehensive book on the fate of drug molecules in the body, including implications for pharmacological and clinical effects. The text provides a unique, balanced approach, examining the specific physical and biological factors affecting the absorption, distribution, metabolism and excretion of drugs, together with mathematical assessment of the concentrations in plasma and body fluids. Understanding the equations requires little more than a basic knowledge of algebra, laws of indices and logarithms, and very simple calculus"-- Provided by publisher. |
| Bibliography note | Includes bibliographical references and index. |
| Source of description | Description based on print version record and CIP data provided by publisher; resource not viewed. |
| Issued in other form | Print version: Curry, Stephen H. Drug disposition and pharmacokinetics Second edition. Hoboken, NJ, USA : Wiley, 2022 9781119588436 |
| LCCN | 2022026799 |
| ISBN | 9781119589235 (epub) |
| ISBN | 1119589231 |
| ISBN | 9781119589198 (adobe pdf) |
| ISBN | 1119589193 |
| ISBN | (cloth) |
