Bayesian parameter estimation and population pharmacokinetics

Abstract

The widespread application of Bayesian parameter estimation in the area of therapeutic drug monitoring (TDM) has prompted the need for well conducted population studies to obtain relevant prior pharmacokinetic parameter estimates. In many cases the population has consisted of a relatively small number of subjects. This may be unavoidable for drugs used in cancer chemotherapy or in small, specific populations of patients. In contrast, information about drugs which are used extensively, such as the aminoglycosides, can be obtained by population studies which involve a large number of individuals. Indeed, this technique has proved particularly useful for determining parameter estimates which can be employed in neonatal TDM. Bayesian parameter estimation has been most frequently used for drugs with narrow therapeutic ranges such as the aminoglycosides, cyclosporin, digoxin, anticonvulsants (especially phenytoin), lithium and theophylline. However, the technique has now been extended to cytotoxic drugs, Factor VIII and warfarin. Bayesian methods have also been used to limit the number of samples required in more conventional pharmacokinetic studies with new drugs. Further advances in the use of these methods are likely to include measures of drug response and toxicity requiring population studies which also include relevant pharmacodynamic information.