ABSTRACT
The term ‘pharmacokinetics’ describes the movement of a drug or medicine around the body, and therefore relates to its absorption from the site of administration, its distribution around the body, and its elimination, usually by either metabolism or excretion. The relationship between the external dose of a drug and the therapeutic response can be divided into two aspects (Fig. 4.1); pharmacokinetics, which relates to the delivery of the chemical to its site of action, and pharmacodynamics, which relates to the interaction between the drug at its site of action and the final therapeutic outcome or pharmacological response. There are a large number of factors that can influence the relationship between the external dose and that delivered to the site of action. The extent of inter-patient variability in pharmacokinetics is similar to the variability in pharmacodynamics,1 so that pharmacokinetics are important in determining the magnitude of clinical response in a patient. Factors that can have a significant influence on pharmacokinetics include age (both
the very young2 and the elderly3), renal and liver disease,4 pregnancy,5,6 gender (to a minor extent in humans7), ethnicity8 and food.9-11 There are major differences in pharmacokinetics between humans and the animal species normally used in toxicity tests,12 so that the interpretation of animal studies and their extrapolation to humans requires considerable expertise.13 The doses used initially in Phase I human studies are normally at least an order of magnitude below doses that do not produce effects in test animals, and the human doses are then escalated until a response is seen. Prediction of the expected pharmacokinetics in humans can increase confidence in dose selection for ‘first-into-man’ studies.
