Pooling plasmas for a rapid answer in pharmacokinetic studies: application to a bioequivalence study of...

Two methods of plasma pooling in pharmacokinetic studies are described. The first method allows the estimation of the average plasma profile of all subjects receiving a given dose or formulation, with at most as many assays as there are time points. The second method allows to estimate the individual AUCs of all subjects with only a single assay for each drug administration. These techniques were successfully employed to predict the final results of a bioequivalence study of two formulations of hydrocortisone 10 mg tablets. Plasma pooling methods can provide early partial information on the results of pharmacokinetic studies. They can be most useful in bioequivalence studies, where early estimates of the average curves and individual AUCs can lead to a decision not to proceed with all the assays, if bioequivalence appears unlikely. The pooling methods may also have useful potential applications in Phase I ascending dose-tolerance studies and in the field of pharmacokinetic studies in small animals. Further studies are necessary to test these methods in order to gain more information on their reliability in the decision-making process in these fields as well as in bioequivalence studies.