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- Title
Gefitinib Increases Serum Concentrations of Oral Irinotecan and SN-38 without Increasing the Biliary Concentration of SN-38 in Rats.
- Authors
Nakamura, Yoichi; Satake, Kurika; Sano, Kazumi; Ito, Akiko; Yoshikawa, Megumi; Ikegami, Yoji; Yoshida, Hisahiro; Nakano, Hirofumi; Oka, Mikio; Sawada, Seigo; Soda, Hiroshi; Kohno, Shigeru
- Abstract
Background: Gefitinib competes with topoisomerase I inhibitors at drug efflux pumps in vitro. We evaluated the effects of oral gefitinib on pharmacokinetic parameters of orally coadministered irinotecan. Methods: We measured the serum pharmacokinetic parameters and biliary excretion of irinotecan, SN-38 and its glucuronide after irinotecan (50 or 100 mg/kg) was orally administered with or without gefitinib 100 mg/kg to rats. We measured the concentrations of irinotecan and SN-38 in the small intestine, liver, lungs and kidneys in each rat. Results: The plasma area under the curve (0–24 h) of irinotecan and SN-38 was increased significantly, while the apparent elimination constant of irinotecan was decreased significantly. Gefitinib significantly increased the biliary cumulative amounts of irinotecan, but not of SN-38, and also influenced the enterohepatic circulation of irinotecan, but not of SN-38. Conclusions: Gefitinib increased the serum concentrations of irinotecan and SN-38 following oral administration of irinotecan without increasing the biliary excretion of SN-38 in vivo. Copyright © 2008 S. Karger AG, Basel
- Subjects
DNA topoisomerase I; DRUG therapy; PHARMACOKINETICS; CHEMICAL kinetics; GLUCURONIDES
- Publication
Chemotherapy (0009-3157), 2008, Vol 54, Issue 6, p485
- ISSN
0009-3157
- Publication type
Article
- DOI
10.1159/000159625