Population based pharmacokinetic analysis: why do we need it; what is it; and what has it told us about anaesthetics?

To study the time course of drug effects in biological systems requires appreciation of drug disposition within the organism; the science of pharmacokinetics. We need also to appreciate how drug effects relate to their concentration in plasma and at the site of action; this is pharmacodynamics. For the specialty of anaesthesia, these two related disciplines have made it possible to understand how anaesthetic drugs can have rapid, profound effects which dissipate rapidly and predictably. Typically, in pharmacokinetics and pharmacodynamics, an empirical mathematical model is defined that describes dr ug effect time cour se after administr ation. That model can then be used mechanistically to predict the action of other doses. Thus, doses and treatment re gimens can be manipulated to optimize the safe and effective use of dr ugs. This is the tr ue use of pharmacokinetics and pharmacodynamics; determination of appropriate dosing regimens. 1 If the mechanistic extrapolation of an empirical pharmacokinetic model developed from data collected in a subject or subjects is reasonable, then we can attempt to predict what will happen in a further subject. In truth, the next subject often does not match our prediction. Of course, we do not expect that all patients respond in a similar manner; there is something missing fr om the