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

Publication ,  Journal Article
Younis, IR; Malone, S; Friedman, HS; Schaaf, LJ; Petros, WP
Published in: Cancer Chemother Pharmacol
February 2009

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.

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Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

February 2009

Volume

63

Issue

3

Start / End Page

517 / 524

Location

Germany

Related Subject Headings

  • Oncology & Carcinogenesis
  • Male
  • Irinotecan
  • Humans
  • Half-Life
  • Glioma
  • Female
  • Enterohepatic Circulation
  • Camptothecin
  • Brain Neoplasms
 

Citation

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Younis, I. R., Malone, S., Friedman, H. S., Schaaf, L. J., & Petros, W. P. (2009). Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Cancer Chemother Pharmacol, 63(3), 517–524. https://doi.org/10.1007/s00280-008-0769-8
Younis, Islam R., Samuel Malone, Henry S. Friedman, Larry J. Schaaf, and William P. Petros. “Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma.Cancer Chemother Pharmacol 63, no. 3 (February 2009): 517–24. https://doi.org/10.1007/s00280-008-0769-8.
Younis IR, Malone S, Friedman HS, Schaaf LJ, Petros WP. Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Cancer Chemother Pharmacol. 2009 Feb;63(3):517–24.
Younis, Islam R., et al. “Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma.Cancer Chemother Pharmacol, vol. 63, no. 3, Feb. 2009, pp. 517–24. Pubmed, doi:10.1007/s00280-008-0769-8.
Younis IR, Malone S, Friedman HS, Schaaf LJ, Petros WP. Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Cancer Chemother Pharmacol. 2009 Feb;63(3):517–524.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

February 2009

Volume

63

Issue

3

Start / End Page

517 / 524

Location

Germany

Related Subject Headings

  • Oncology & Carcinogenesis
  • Male
  • Irinotecan
  • Humans
  • Half-Life
  • Glioma
  • Female
  • Enterohepatic Circulation
  • Camptothecin
  • Brain Neoplasms