All the basic concepts of pharmacokinetics (PKs) are described, with an emphasis on understanding what parameters such as bioavailability, volume of distribution and clearance tell us about the behaviour of a particular drug. The use of PKs in both a drug development and a clinical setting are covered. The essential mathematical basis of PKs is explained, but excessive mathematical complexity is avoided. For all key equations, practical examples of their use are provided. There are plenty of practice questions (along with model answers). Additional spreadsheets are provided online.
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- ADME and Pharmacokinetics
- ADME – Absorption Distribution, Metabolism and Excretion
- Pharmacokinetics
- Absorption: Absorption rate constant, Bioavailability and Salt factor
- Passive diffusion and other mechanisms by which drugs may cross biological membranes
- Rate of drug absorption and the Absorption rate constant (Ka)
- Bioavailability
- Salt factor
- Distribution: Compartments and Volume of Distribution
- The rate of distribution and compartments
- One compartment model
- Two compartment model
- The extent of distribution
- Volume of distribution
- Using the volume of distribution to calculate dose size
- Practice calculations
- Elimination: Elimination rate constant, half-life and clearance
- Elimination rate constant and half-life
- Clearance
- Practice calculations
- Single intravenous bolus injection into one compartment
- Concentration versus time graph
- Relationship between time and concentration
- Area Under the Curve (AUC)
- Practice calculations
- Appendix 1
- Appendix 2
- Analysis of experimental data from a bolus i.v
- injection into one compartment
- Analysis of clinical trials data
- Analysis of data arising in a clinical setting
- Practice calculations
- Appendix 1
- Appendix 2
- Single intravenous bolus injection into two compartments
- The model to be considered
- Drug concentrations in blood and the rest of the first compartment
- Determining how many compartments a drug occupies
- Drug concentration in the second compartment
- Two compartment systems and therapeutic drug monitoring for digoxin
- Constant intravenous infusion
- The model to be considered
- Concentration versus time curve during infusion
- Relationship between rate of infusion and concentration at steady state
- Loading doses
- The accumulation period
- Practice questions
- Appendix
- Extravascular administration
- The situation to be considered
- Concentration versus time curve
- Changing the rate of absorption
- Cmax and Tmax
- Determination of bioavailability for extravascular doses
- Trapezoidal rule – A practical method to measure AUC
- Practice question
- Appendix
- Multiple dosing
- Pharmacokinetic accumulation and steady state
- Multiple extravascular doses
- Concentrations at steady state
- Loading dose
- Accumulation stage
- Extent of fluctuation in drug concentrations
- Practice questions
- Appendix
- Non-linear pharmacokinetics
- Considering drug metabolism as an enzyme catalysed reaction
- Exceptions to linearity
- Effect of non-linearity on the relationship between dose and drug concentration
- Clinical significance of non-linear kinetics
- Non-linear kinetics and drug development
- Non-compartmental pharmacokinetics
- The case for non-compartmental methods
- Calculation methods
- More complex situations
- Computerized analysis of pharmacokinetic data
- Least squares fitting
- Practice question
- Creatinine clearance
- Clearance of creatinine and various drugs
- Digoxin dosing
- Practice questions
- Pharmacokinetic symbols and equations
- Symbols
- Cockcroft and Gault equations
- Additional material available from the internet
- Answers to practice questions
C'est livre très intéressent.
This is a good reinforcement especially for me that I find Pharmacology quite difficult. It's detailed yet direct to the point that perfectly matches a student's level of understanding.