吉西他滨固定速率输注的峰浓度与血液学毒性的相关性研究

Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile

目的：研究吉西他滨2h固定速率输注在非小细胞肺癌（NSCLC）患者中的峰浓度（Cmax）与血液学毒性的相关性。方法：选择21例患者，吉西他滨（1200mg／m^2）2h固定速率静脉输注联合卡铂的给药方案。采用离子对反相高效液相色谱法测定吉西他滨血药浓度。结果：吉西他滨平均Cmax为（4．95±2．42）μg·ml^-1。血液学毒性主要为Ⅲ～Ⅳ级的血小板和中性粒细胞减少症。白细胞计数平均下降百分率为（38．3±38．1）％，中性粒细胞计数下降（31．3±73．6）％，血小板计数下降（31．8±53．5）％，血红蛋白下降（12．0±12．2）％.Cmax与白细胞计数下降百分率存在相关性（r^2=0．4575，P〈0．05），同样Cmax与血小板计数下降百分率存在相关性（r^2=0．5671，P〈0．05）。结论：作为治疗NSCLC一线的有效化疗方案，患者对其血液学毒性可以耐受，治疗有较好的依存性。对Cmax与血液学毒性的相关性研究，为吉西他滨个体化给药，从而为减少不良反应提供了依据。

Objective： To investigate the relationship between peak concentration （Cmax） Of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer （NSCLC）. Methods： Twenty-one patients received gemcitabine at a fixed dose rate （1 200 mg/m^2 over 120 min） with carboplatin. Plasma concentrations of gemcitabine were measured by ion-pair reversed-phase high-performance liquid chromatography. Results： The mean value of Cmax in 21 eligible patients was （4. 95±2.42）μg · ml^-1. The main hematological toxicity was grade Ⅲ- Ⅳ thrombocytopenia and neutropenia. The mean percentages of reduction of WBC,NEC,PLTC and Hb of 21 patients were （38.3±38.1）%, （31.3 ±73.6）%, （31.8±53.5）% and （12.0±12.2）% ,respectively. The Cmax of gemcitabine and the percentage of reduction in WBC showed a significant correlation （r^2= 0. 4575,P〈0. 05）. A significant correlation（r^2= 0. 5671,P〈0. 05）was also observed between the percentage of reduction of PLTC and Cmax Of gemcitabine. Conclusion： The results of relationship between Cma x and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR.