Optimal statistical design for toxicokinetic studies.

Abstract

Optimal statistical design strategies are applied to toxicokinetic experiments, for determining proper allocations of subjects and/or spacings of sampling times under a variety of nonlinear concentration-time models. The strategies include: (i) optimal allocations of subjects assuming the placement of time points is fixed, (ii) optimal spacing of design time points while assuming an equal allocation of subjects per time points and (iii) allocations/time-point spacings optimized jointly. Emphasis is placed on the first case, where a variance-minimization method is illustrated for optimizing the allocations when estimating specific toxicokinetic parameters. Appeals to forms of D-optimality are also considered, for cases when no specific toxicokinetic parameter is of specialized interest.