Etienne M C, Chatelut E, Pivot X, Lavit M, Pujol A, Canal P, Milano G
Oncopharmacology Laboratory, Centre Antoine Lacassagne, Toulouse, France.
Eur J Cancer. 1998 Jan;34(1):92-7. doi: 10.1016/s0959-8049(97)00345-6.
The objective of this study was to attempt to identify patient co-variables which could influence interpatient variability in 5-fluorouracil (5-FU) clearance during a 5-day continuous venous infusion (CVI, cisplatin 100 mg/m2 day 1 then 5-FU 1 g/m2/day days 2-6). The analysis was performed using a NONMEM program according to a linear one-compartment model. A total of 186 cycles (2 samples per day, 8 a.m. and 5 p.m.) were analysed from 104 patients with various cancers (the majority of head and neck and oesophagus). The study co-variables were age, sex, body surface area, hepatic metastases, peripheral mononuclear cell dihydropyrimidine dehydrogenase activity (PMNC-DPD), liver enzymes, clock-time (8 a.m. versus 5 p.m.), elapsed time during CVI. The data showed that 5-FU clearance was significantly reduced by increased age, low PMNC-DPD, high serum alkaline phosphatase and elapsed time during infusion. These data may be useful for improving knowledge of predictive factors which can influence 5-FU exposure and thus predispose to toxic manifestations.
本研究的目的是试图确定在5天持续静脉输注（CVI，第1天顺铂100mg/m²，然后第2 - 6天5-氟尿嘧啶1g/m²/天）期间可能影响患者间5-氟尿嘧啶（5-FU）清除率差异的患者协变量。根据线性一室模型使用NONMEM程序进行分析。共分析了104例患有各种癌症（大多数为头颈癌和食管癌）患者的186个疗程（每天2个样本，上午8点和下午5点）。研究的协变量包括年龄、性别、体表面积、肝转移、外周血单核细胞二氢嘧啶脱氢酶活性（PMNC-DPD）、肝酶、时间点（上午8点与下午5点）、CVI期间的 elapsed time。数据显示，年龄增加、PMNC-DPD低、血清碱性磷酸酶高和输注期间的elapsed time会显著降低5-FU清除率。这些数据可能有助于提高对可影响5-FU暴露从而易导致毒性表现的预测因素的认识。
