Comments on the Statistical Analysis of Toxicokinetic Studies

Abstract

This paper provides a brief review of the properties shared by chemical kinetics, clinical pharmacokinetics, and toxicokinetics and on where they differ. The special situation of toxicokinetics and some methods for estimating secondary pharmacokinetic parameters are discussed. The focus is on the application of resampling techniques to toxicokinetic studies and a comparison to the classical approaches. In many cases resampling techniques enjoy the advantage of being easy to perform and easy to adapt to new designs, and there is generally no need to fit the data to certain distributions. Complicated theoretical calculations can be circumvented and new methods, for example, of area under the data (AUD) calculation, may be incorporated without substantial effort. Two resampling techniques, the pseudo-profile based bootstrap and the pooled data bootstrap, are outlined. One of the appealing features of the pseudo-profile based bootstrap is the possibility of estimating summary statistics on the basis of individual secondary pharmacokinetic parameter estimates.