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.
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UMR 181, Physiopathologie et Toxicologie Expérimentales, Ecole Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
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D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects; D019772:Topotecan / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D000970:Antineoplastic Agents; D019772:Topotecan