Comparisons of the pharmacokinetics and the leukopenia and thrombocytopenia grade after administration of irinotecan and 5-fluorouracil in combination to rats

Background: Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). Preliminary dat a on this combination therapy in humans demonstrated no drug interactions b etween CPT-11 (or its metabolite, SN-38) and 5-FU however, because there is so little information on the combination the possibility for an interactio n still exists. Material and Methods: CPT-11 and 5-FU were injected intrave nously into mts and the pharmacokinetics of CPT-11 and SN-38 and alternatio ns in blood cell count were investigated. Results: In the group of rats adm inistered 5-FU prior to CPT-11, the area under the concentration-time curve (AUC) of CPT-11 was approximately eigh-fold larger compared with the group administered CPT-11 prior to 5-FU. On the other hand, the grade of leukocy topenia or thrombocytopenia was not significantly different among the two g roups. Conclusion: In mts, the conversion of CPT-11 into SN-38 is possibly delayed by prior administration of 5-FU.