Population pharmacokinetics/pharmacodynamics relationships of an anticancer drug.

This paper proposes a method for studying the toxicity of an anticancer drug with a delayed effect. The goal is to predict a dosage regimen with controlled toxicity. To this end, a semi-physiological model is used. A limit of toxicity is demonstrated, which is intrinsic to the model. It reduces the effect of high drug concentrations. This limit explains the mixed behaviour of the drug: time-dependence and concentration-dependence, according to the dose actually administered. A population analysis is performed to estimate the parameters of the model, and to predict a safe dosage regimen.