Simulation tool for schedule-dependent etoposide exposure based on pharmacokinetic findings published in the literature

It is the aim of this study to establish a simulation tool for etoposide (E to) which can be used to interpret drug monitoring data in clinical practic e and to design new schedules for future protocols. As schedule dependency was observed for Eto, knowledge of concentration-time profiles is important . Pharmacokinetic data from children after low-dose i.v. administration of Eto together with data reported in the literature were used to construct th e simulation tool. Validation was performed by independently reproducing va rious published data. Dose linearity of AUC was shown over the whole dose r ange of 20-2000 mg/m(2) reported in the literature and fits the predictions by the simulation tool. There was no difference in clearance between child ren and adults. Close agreement was found between predicted and reported co ncentration-time profiles after various administration schedules. However, subgroups with significantly altered pharmacokinetics of Eto, such as patie nts with renal impairment or concurrent cisplatin chemotherapy, were exclud ed from the comparisons. In these patients values predicted for a 'regular' patient might be used as a base for possible dose modifications. In summar y, a pharmacokinetic model of high predictive value is presented which allo ws simulations of Eto concentration-time profiles for low- as well as high- dose conditions and various infusion times. [(C) 2001 Lippincott Williams & Wilkins.].