Includes bibliographical references and indexes.

Intro
Atkinson's Principles of Clinical Pharmacology
Copyright
Contents
Contributors
Preface to the first edition
Preface to the fourth edition
Chapter 1: Introduction to clinical pharmacology
Background
Optimizing use of existing medicines
Evaluation and development of medicines
Pharmacokinetics
The concept of clearance
Clinical estimation of renal function
Dose-related toxicity often occurs when impaired renal function is unrecognized
References
Additional sources of information
Chapter 2: Clinical pharmacokinetics
The target concentration strategy
Monitoring serum concentrations of digoxin as an example
General indications for drug concentration monitoring
Concepts underlying clinical pharmacokinetics
Initiation of drug therapy (concept of apparent distribution volume)
Continuation of drug therapy (concepts of elimination half-life and clearance)
Elimination half-life
Elimination clearance
Drugs not eliminated by first-order kinetics
Mathematical basis of clinical pharmacokinetics
First-order elimination kinetics
Concept of elimination half-life
Relationship of k to elimination clearance
Cumulation factor
The plateau principle
Application of Laplace transforms to pharmacokinetics
References
Study problems
Chapter 3: Compartmental analysis of drug distribution
Fit-for-purpose modeling of drug distribution
Physiological significance of drug distribution volumes
Physiological basis of multicompartmental models of drug distribution
Formulation of multicompartmental models
Basis of multicompartmental structure
Mechanisms of transcapillary exchange
Clinical consequences of different drug distribution patterns
Drugs with faster elimination than distribution
Estimating model parameters from experimental data. Derivation of equations for a two-compartment model
Calculation of rate constants and compartment volumes from data
Different estimates of apparent volume of distribution
References
Study problems
Chapter 4: Drug absorption and bioavailability
Drug absorption
Metabolism by intestinal bacteria
Presystemic elimination
Drug-drug and food-drug interactions
Bioavailability
Absolute bioavailability
Relative bioavailability
In vitro prediction of bioavailability
Kinetics of drug absorption after oral administration
Time to peak level
Value of peak level
Use of convolution/deconvolution to assess in vitro-in vivo correlations
References
Study problems
Chapter 5: Effect of kidney disease on pharmacokinetics
Drug dosing in patients with impaired kidney function
Effects of kidney disease on renal drug elimination mechanisms
Excretion mechanisms: Filtration and secretion
Reabsorption mechanisms
Renal metabolism
Analysis and interpretation of renal excretion data
Effects of impaired kidney function on nonrenal clearance pathways
Nonrenal metabolism
Nonrenal transport
Potential mechanisms of altered nonrenal clearance
Effects of kidney disease on drug distribution
Plasma protein binding of acidic drugs
Plasma protein binding of basic and neutral drugs
Tissue binding of drugs
Effects of kidney disease on drug absorption
Study problem
References
Chapter 6: Pharmacokinetics in patients requiring renal replacement therapy
Kinetics of intermittent hemodialysis
Solute transfer across dialyzing membranes
Calculation of dialysis clearance
Patient factors affecting hemodialysis of drugs
Hemodynamic changes during Dialysis
Kinetics of CRRT and sustained renal replacement therapy
Clearance by continuous hemofiltration. Clearance by continuous hemodialysis and SLED
Extracorporeal clearance during continuous renal replacement therapy
Clinical considerations
Drug dosing guidelines for patients requiring renal replacement therapy
Extracorporeal therapy of patients with drug toxicity
References
Chapter 7: Effect of liver disease on pharmacokinetics
Physiologic determinants of hepatic drug clearance
Hepatic elimination of drugs
Restrictively metabolized drugs (ER0.3)
Effect of changes in protein binding on hepatic clearance
Effect of changes in intrinsic clearance on hepatic drug clearance
Drugs with an intermediate extraction ratio (0.3ER0.7)
Nonrestrictively metabolized drugs (ER0.70)
Biliary excretion of drugs
Enterohepatic circulation
Effects of liver disease on pharmacokinetics
Acute hepatitis
Chronic liver disease and cirrhosis
Pharmacokinetic consequences of liver cirrhosis
Influence of portosystemic shunting on nonrestrictively metabolized drugs
Consequences of decreased protein binding
Consequences of hepatocellular changes
Use of therapeutic drugs in patients with liver disease
Classification schemes for liver function
FDA guidance for industry on pharmacokinetic studies in patients with impaired hepatic function
Other tools for the assessment of liver function
Effects of liver disease on the hepatic elimination of drugs
Correlation of laboratory tests with drug metabolic clearance
Use of probe drugs to characterize hepatic drug clearance
Effects of liver disease on the renal elimination of drugs
Effects of liver disease on patient response
Modification of drug therapy in patients with liver disease
References
Chapter 8: Noncompartmental and compartmental approaches to pharmacokinetic data analysis
Introduction. Kinetics, pharmacokinetics, and pharmacokinetic parameters
Kinetics and the link to mathematics
The pharmacokinetic parameters
Accessible pool parameters
System parameters
Moments
Noncompartmental analysis
Noncompartmental model
Kinetic parameters of the noncompartmental model
The single accessible pool model
The two accessible pool model
Estimating the kinetic parameters of the noncompartmental model
Estimating AUC and AUMC using sums of exponentials
Estimating AUC and AUMC using other functions
Estimating t1tnC(t)dt and t1tntC(t)dt
Extrapolating from tn to infinity
Estimating AUC and AUMC from 0 to infinity
Compartmental analysis
Definitions and assumptions
Linear, constant coefficient compartmental models
Parameters estimated from compartmental models
Experimenting on compartmental models: Input and measurements
Nonlinearities in compartmental models
Calculating pharmacokinetic parameters from a compartmental model
Model parameters
Residence time calculations
Noncompartmental versus compartmental models
Models of data vs. models of system
The equivalent sink and source constraints
Linearity and time invariance
Recovering pharmacokinetic parameters from compartmental models
Conclusion
References
Chapter 9: Population pharmacokinetics
Introduction
Analysis of pharmacokinetic data
Structure of pharmacokinetic models
Fitting individual data
Population pharmacokinetics
Population analysis methods
The naïve pooled data method
The two-stage method
Nonlinear mixed effects modeling method
Model comparison
Model evaluation
Model applications
Mirogabalin case study
Milademetan case study
Conclusions
References
Chapter 10: Pathways of drug metabolism
Introduction. The chemistry and enzymology of drug metabolism
Oxidations and nonconjugation reactions
Cytochrome P450 monooxygenases
Cytochrome P450 families
The CYP3A family
The CYP2C family
The CYP2D6 family
The CYP 1A family
Non-CYP oxidations
Flavin-containing monooxygenases
Monoamine oxidases
Molybdenum-containing oxidases
Esterases
Epoxide hydrolases
Conjugation reactions
Glucuronosyl transferases
Sulfotransferases
Acetyl transferases
Methyltransferases
Glutathione transferases
References
Chapter 11: Bioanalytical methods: Technological platforms and method validation
Technological platforms of bioassays
High performance/pressure liquid chromatography
Chromatographic column
Mobile phase
Detectors
Alternative chromatographic approaches
Gas chromatography
LC-MS/MS and high resolution mass spectrometry (HRMS)
Internal standards
Accelerator mass spectrometry
Immunoassays
Polymerase chain reaction assays
Method validation
Sample analysis
Cross-validation
Case examples
Interference
Establishing assay range
Impact of sample handling or instability
Assessing results from two assays: Cross-validation
Conclusion
References
Chapter 12: Clinical pharmacogenetics
Introduction
General principles
Pharmacogenetics and pharmacogenomics
Human genetics
Indications for performing pharmacogenetic studies
Genetic analysis techniques and informatics
Examples of clinically relevant genetic polymorphisms
Genetic variation in Phase I metabolic pharmacogenes
CYP2B6
CYP2C9
CYP2C19
CYP2D6
CYP3A4 and CYP3A5
Genetic variation in Phase II metabolic pharmacogenes
Thiopurine S-methyltransferase (TPMT)
N-Acetyltransferase 2 (NAT2)
Target/efficacy pharmacogenetics

"Atkinson's Principles of Clinical Pharmacology, Fourth Edition is the essential reference on the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development. This well-regarded survey continues to focus on the basics of clinical pharmacology for the development, evaluation and clinical use of pharmaceutical products while also addressing the most recent advances in the field. Written by leading experts in academia, industry, clinical and regulatory settings, the fourth edition has been thoroughly updated to provide readers with an ideal reference on the wide range of important topics impacting clinical pharmacology"--