The Use Of A Stochastic Model For Data Exhibiting Heterogeneous Pharmacokinetics
L.Claret(1), P.Macheras(2), N.Simon(3), A.Iliadis(4)
(1)Pharsight Corporation, Argentum, 2 Queen Caroline Street, Hammersmith, London W6 9DT
A stochastic compartmental model was developed to describe heterogeneous elimination kinetics of drugs. It is a probabilistic transfer model with a gamma distributed probability intensity coefficient for drug elimination. This model was compared to the traditional compartmental deterministic model in a population analysis of cyclosporin data from 52 patients receiving cyclosporin as a 2-hr intravenous infusion. Several methods (FOCE, two-stage) were used to estimate model parameters. The results showed that the stochastic model, although simpler than the compartmental deterministic models, is more flexible and consistent, and gives a better fit to the kinetic data of cyclosporin than the compartmental deterministic models.