Optimal sampling times for pharmacokinetic experiments.

A sequential estimation procedure is presented which uses optimal sampling times to estimate the parameters of a model from data obtained from a group of subjects. This optimal sampling sequential estimation procedure utilizes parameter estimates from previous subjects in the group to determine the optimal sampling times for the next subject. Parameter estimates obtained from the optimal sampling procedure are compared to those obtained from a conventional sampling scheme by using Monte Carlo simulations which include noise terms for both assay error and intersubject variability. The results of these numerical experiments, for the two examples considered here, show that the parameter estimates obtained from data collected at optimal sampling times have significantly less variability than those generated using the conventional sampling procedure. We conclude that optimal sampling and preexperiment simulation may be useful tools for designing informative pharmacokinetic experiments.