Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Anticancer Res. 2013 Sep;33(9):3845-53.
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.
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.
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.
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.
我们评估了转移性结直肠癌患者接受 CPT-11/S-1（IRIS）或 5-氟尿嘧啶（5-FU）/亚叶酸（LV）/CPT-11（FOLFIRI）方案治疗时，伊立替康（CPT-11）及其代谢物的药代动力学。
IRIS 和 FOLFIRI 方案之间以及给药第 1 天和第 15 天之间比较了血清 CPT-11、SN-38（CPT-11 的活性代谢物）和 SN-38-葡萄糖醛酸苷的浓度。还评估了药代动力学数据与中性粒细胞减少和腹泻发生率之间的相关性。
CPT-11 或其代谢物的药代动力学在第 1 天和第 15 天之间没有显著差异。SN-38 浓度与中性粒细胞减少的发生相关，FOLFIRI 组的中性粒细胞减少发生率明显高于 IRIS 组。
重复 IRIS 或 FOLFIRI 给药后 CPT-11 的药代动力学没有改变。FOLFIRI 组中性粒细胞减少的发生率高于 IRIS 组，因为前者 SN-38 的暴露量更大。
