Atkinson's principles of clinical pharmacology.

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Detalles Bibliográficos
Clasificación:Libro Electrónico
Otros Autores: Huang, Shiew-Mei (Editor ), Lertora, Juan (Editor ), Vicini, Paolo (Editor ), Atkinson, Arthur J., Jr (Editor )
Formato: Electrónico eBook
Idioma:Inglés
Publicado: London, United Kingdom : Academic Press, [2022]
Edición:Fourth edition /
Temas:
Clinical pharmacology.
Pharmacology, Clinical
Pharmacologie clinique.
Clinical pharmacology
Acceso en línea:Texto completo
Tabla de Contenidos:
  • 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 n�ave 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.

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