"Pharmacokinetics" by Philip Rowe

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.

Contents
Introduction
1.ADME and Pharmacokinetics
1.1. ADME – Absorption Distribution, Metabolism and Excretion
2.2. Pharmacokinetics
2. Absorption: Absorption rate constant, Bioavailability and Salt factor
2.1. Passive diffusion and other mechanisms by which drugs may cross biological membranes
2.2. Rate of drug absorption and the Absorption rate constant (Ka)
2.3 Bioavailability
2.4 Salt factor
3 Distribution: Compartments and Volume of Distribution
3.1 The rate of distribution and compartments
3.2 One compartment model
3.3 Two compartment model
3.4 The extent of distribution
3.5 Volume of distribution
3.6 Using the volume of distribution to calculate dose size
3.7 Practice calculations
4 Elimination: Elimination rate constant, half-life and clearance
4.1 Elimination rate constant and half-life
4.2 Clearance
4.3 Practice calculations
5 Single intravenous bolus injectionin to one compartment
5.1 Concentration versus time graph
5.2 Relationship between time and concentration
5.3 Area Under the Curve (AUC)
5.4 Practice calculations
5.5 Appendix 1: Derivation of the equations t½ = 0.693 / K and K = 0.693 / t½
5.6 Appendix 2: Derivation of the equation: AUC = F.D / Cl
6 Analysis of experimental data from a bolus i.v. injection into one compartment
6.1 Analysis of clinical trials data
6.2 Analysis of data arising in a clinical setting
6.3 Practice calculations
6.4 Appendix 1
6.5 Appendix 2: Derivation of the equation K = Ln(C1/C2) / (T2-T1)
7 Single intravenous bolus injectionin to two compartments
7.1 The model to be considered
7.2 Drug concentrations in blood and the rest of the first compartment
7.3 Determining how many compartments a drug occupies
7.4 Drug concentration in the second compartment
7.5 Two compartment systems and therapeutic drug monitoring for digoxin
8 Constant intravenous infusion
8.1 The model to be considered
8.2 Concentration versus time curve during infusion
8.3 Relationship between rate of infusion and concentration at steady state
8.4 Loading doses
8.5 The accumulation period
8.6 Practice questions
8.7 Appendix: Derivation of the equation Css = Rinf / Cl
9 Extravascular administration
9.1 The situation to be considered
9.2 Concentration versus time curve
9.3 Changing the rate of absorption
9.4 Cmax and Tmax
9.5 Determination of bioavailability for extravascular doses
9.6 Trapezoidal rule – A practical method to measure AUC
9.7 Practice question
10 Multiple dosing
10.1 Pharmacokinetic accumulation and steady state
10.2 Multiple extravascular doses
10.3 Concentrations at steady state
10.4 Loading dose
10.5 Accumulation stage
10.6 Extent of fluctuation in drug concentrations
10.7 Practice questions
11 Non-linear pharmacokinetics
11.1 Considering drug metabolism as an enzyme catalysed reaction
11.2 Exceptions to linearity
11.3 Effect of non-linearity on the relationship between dose and drug concentration
11.4 Clinical significance of non-linear kinetics
11.5 Non-linear kinetics and drug development
12 Non-compartmental pharmacokinetics
12.1 The case for non-compartmental methods
12.2 Calculation methods
12.3 More complex situations
13 Computerized analysis of pharmacokinetic data
13.1 Least squares fitting
13.2 Practice question
14 Creatinine clearance
14.1 Clearance of creatinine and various drugs
14.2 Digoxin dosing
14.3 Practice questions
Pharmacokinetic symbols and equations
Additional material available from the internet
Answers to practice questions

www.dfiles.eu/files/cwk1qafu7