Pharmacokinetic assessment of irinotecan, SN-38, and SN-38-glucuronide: a substudy of the FIRIS study.

BACKGROUND

We evaluated the pharmacokinetics of irinotecan (CPT-11) and its metabolites in patients with metastatic colorectal cancer receiving the combination of CPT-11/S-1 (IRIS) or 5-fluorouracil (5-FU)/l-leucovorin (LV)/CPT-11 (FOLFIRI) regimens in the FIRIS trial.

PATIENTS AND METHODS

Serum CPT-11, SN-38 (an active metabolite of CPT-11), and SN-38-glucuronide concentrations were compared between the IRIS and FOLFIRI regimens, and between days 1 and 15 of administration. Correlations between pharmacokinetic data and incidence of neutropenia and diarrhea were also assessed.

RESULTS

There were no significant differences in the pharmacokinetics of CPT-11 or its metabolites between days 1 and 15. SN-38 concentrations were correlated with the occurrence of neutropenia, which was significantly more frequent in the FOLFIRI group than in the IRIS group.

CONCLUSION

No alterations in CPT-11 pharmacokinetics after repeated IRIS or FOLFIRI administration were observed. Neutropenia was more frequent in the FOLFIRI group than in the IRIS group because exposure to SN-38 was greater in the former group.