Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma.
Journal Article (Journal Article)
BACKGROUND: Enterohepatic recirculation of irinotecan and one of its metabolites, SN-38, has been observed in pharmacokinetic data sets from previous studies. A mathematical model that can incorporate this phenomenon was developed to describe the pharmacokinetics of irinotecan and its metabolites. PATIENTS AND METHODS: A total of 32 patients with recurrent malignant glioma were treated with weekly intravenous administration of irinotecan at a dose of 125 mg/m(2). Plasma concentrations of irinotecan and its three major metabolites were determined. Pharmacokinetic models were developed and tested for simultaneous fit of parent drug and metabolites, including a recirculation component. RESULTS: Rebound in the plasma concentration suggestive of enterohepatic recirculation at approximately 0.5-1 h post-infusion was observed in most irinotecan plasma concentration profiles, and in some plasma profiles of the SN-38 metabolite. A multi-compartment model containing a recirculation chain was developed to describe this process. The recirculation model was optimal in 22 of the 32 patients compared to the traditional model without the recirculation component. CONCLUSION: A recirculation chain incorporated in a multi-compartment pharmacokinetic model of irinotecan and its metabolites appears to improve characterization of this drug's disposition in patients with glioma.
- Younis, IR; Malone, S; Friedman, HS; Schaaf, LJ; Petros, WP
- February 2009
Volume / Issue
- 63 / 3
Start / End Page
- 517 - 524
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)