Optimal Designs for Non-Compartmental Analysis of Pharmacokinetic Studies

Abstract

ABSTRACTIn traditional toxicology trials, pharmacokinetics (PK) is investigated in the satellite group of animals, and the pharmacodynamics (PD) is investigated in the study group of animals. The new blood sampling method of microsampling opens up the opportunity to investigate both PK and PD in the same animals. To avoid excessive burden on the animals from the required blood sampling, sparse sampling schemes are typically used. Motivated by this application, this article introduces a procedure to choose an optimal sparse sampling scheme and sampling time points using non-compartmental methods but which can be applied to further settings beyond this. We discuss how robust designs can be obtained and we apply and evaluate the approach to a range of scenarios to give an example of how it may be implemented. The results are compared to optimal designs for model based PK. Supplementary materials for this article are available online.