紫杉醇用于非小细胞肺癌的药代动力学与疗效、毒性反应关系研究

目的寻找紫杉醇用于非小细胞肺癌的药代动力学参数与疗效和毒性反应之间的关系。方法 10例非小细胞肺癌患者采用紫杉醇135～175 mg·m-2第1天,静滴3 h,联合顺铂20 mg·d-1第1～5天方案化疗,动态采集血样本,利用HPLC方法测定血药浓度,计算药代动力学参数。记录用药过程中不良反应和疗效评价结果。采用SPSS 19.0统计学方法和DAS 3.0药物动力学软件进行数据分析。结果肝功能损害组Cmax高于无肝功能损害组,且有统计学意义(P=0.012);疾病控制组的每平方米体表面积药量(Dose)高于疾病进展组,差异有统计学意义(P=0.02)。白细胞减少组Dose、AUC、Cmax、t(>0.1)和t(>0.05)等均高于无白细胞减少组,但差异无统计学意义(P>0.05);白细胞减少组t1/2a低于无白细胞减少组,差异有统计学意义(P=0.034)。结论疾病控制组、白细胞减少组和肝损害组AUC分别高于疾病进展组,无白细胞减少组和无肝损害组;且白细胞减少组和肝损害组Cmax分别高于无白细胞减少组和无肝功能损害组,因此可以将紫杉醇AUC和Cmax作为观察疗效和毒副反应的指标,为临床个体化治疗提供一定的理论支持。

Clinical pharmacokinetic-pharmacodynamic of paclitaxel in non-small cell lung cancer

Objective To define a pharmacodynamic relationships between paclitaxel disposition and its toxicity and efficacy in non-small cell lung cancer patients. Methods Paclitaxel pharmacokinetics and pharmacodynamies were studied in 10 patients with non-small cell lung cancer. Paclitaxel was administered at 135 - 175 mg . m-2 by a 3-hour infusion schedule in the first day ,followed by cisplatin 20 mg . d-1 for 5 days. The toxicity and efficacy in the process of treatment were recorded. The data were analyzed by SPSS 19.0 statistical methods and medicine dynamics software DAS 3.0. Results Investigation of pharmacodynamics showed that Cmax was higher in the hepatotoxicity group, and had a statistical significance （P = 0. 012）. Dose of every square metre surface area in the disease control group was higher than the disease progress group, and the difference was statistically significant （P = 0.02）. And also AUC, Cmax and drugs in threshold concentration （ C 〉 0.1 umol . L- 1 or 0.05 umol . L-1 ） maintain time were higher in the leucopenia group, but there was no statistical significace （P 〉 0.05 ）. The t1/2a was lower in the leucopenia group, and the difference was statistically significant （P = 0.034 ）. Conclusions AUC was higher in the disease control,leueopenia and liver damage group, and Cmax was higher in the leucopenia and liver damage group, therefore AUC and Crux may be conducted as an index for paclitaxel curative effect and toxicity, and provide some theoretical supports for clinical individual therapy.