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Cancer Chemotherapy and Pharmacology

Published in:

01-02-2009 | Original Article

Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma

Authors: Islam R. Younis, Samuel Malone, Henry S. Friedman, Larry J. Schaaf, William P. Petros

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2009

Abstract

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/m². 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.

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Title: Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma
Authors: Islam R. Younis
Samuel Malone
Henry S. Friedman
Larry J. Schaaf
William P. Petros
Publication date: 01-02-2009
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-008-0769-8

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Abstract

Background

Patients and methods

Results

Conclusion

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