Department of Clinical Pharmacy and Diagnostics, Center of Pharmacy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Anticancer Res. 2011 Oct;31(10):3573-8.
Biotransformation of irinotecan (CPT-11) into its pharmacologic active metabolite SN-38 was investigated in patients treated for advanced colorectal cancer. A dose of 180 mg/m(2) CPT-11 was administered to 6 patients by 60 min hepatic intra-arterial infusion (HAI) via a surgically implanted Port-a-Cath® system. Blood samples were collected from 0 to 360 min after start of HAI, and CPT-11 plus metabolites were analysed by a selective reversed phase HPLC method. The objective of this study was to evaluate the extent to which SN-38 is generated after HAI of irinotecan given at a low dose of 180 mg/m(2). In a second investigation, CPT-11 was administered via conventional intravenous infusion (dose 180 mg/m(2), 60 min infusion time, 11 patients) and CPT-11 plus metabolites were quantified using identical analytical procedure. Compared to i.v. infusion, the pharmacokinetics of CPT-11 and SN-38 were altered by HAI. The mean c(max) of CPT-11 after HAI was reduced by 37%, whereas the mean c(max) of SN-38 increased by 60%. HAI resulted in a desired, increased metabolic conversion of CPT-11 into SN-38 and might improve the regional availability of the pharmacologic active metabolite SN-38 at the site of tumor. Plasma concentrations of the metabolites SN-38 glucuronide and APC remained unaffected by the route of administration.
在接受晚期结直肠癌治疗的患者中，研究了伊立替康（CPT-11）转化为其药理活性代谢物 SN-38 的情况。6 名患者通过手术植入的 Port-a-Cath®系统以 60 分钟的肝内动脉输注（HAI）方式接受 180mg/m²CPT-11 的剂量。在 HAI 开始后 0 至 360 分钟采集血样，并通过选择性反相 HPLC 方法分析 CPT-11 加代谢物。本研究的目的是评估在低剂量 180mg/m² 给予伊立替康 HAI 后 SN-38 的生成程度。在第二项研究中，通过常规静脉输注（剂量 180mg/m²，60 分钟输注时间，11 名患者）给予 CPT-11，并使用相同的分析程序定量 CPT-11 加代谢物。与静脉输注相比，CPT-11 和 SN-38 的药代动力学通过 HAI 发生改变。HAI 后 CPT-11 的平均 c(max)降低了 37%，而 SN-38 的平均 c(max)增加了 60%。HAI 导致 CPT-11 向 SN-38 的代谢转化增加，这可能提高肿瘤部位药理活性代谢物 SN-38 的局部可用性。代谢物 SN-38 葡萄糖醛酸苷和 APC 的血浆浓度不受给药途径的影响。
