卡铂按不同AUC给药对晚期卵巢上皮癌患者药动学参数的影响

Effects of Carboplatin Administration on Pharmacokinetic Parameters according to AUC in Advanced Epithelial Ovarian Cancer Patients

目的:为指导卡铂的合理使用和个体化治疗提供参考。方法:采用高效液相色谱-紫外法。色谱柱为Kromasil C18柱,流动相为H2O,柱温为30℃,流速为1 ml/min,检测波长为230 nm,进样量为50μl。选择符合条件的晚期卵巢上皮癌患者10例,均分为两组,分别使用两种剂量卡铂(AUC=4或AUC=6)联合紫杉醇进行化疗;以尿苷为内标物,测定血浆中卡铂的质量浓度,绘制药-时曲线,计算两组药动学参数。结果:血浆中卡铂检测质量浓度在1.56～100μg/ml范围内同卡铂与内标物峰面积之比呈良好的线性关系(r=0.999 0);卡铂平均相对回收率为98.91%,RSD=3.96%(n=5);两种给药剂量下的单次给药计算出的卡铂的药动学参数AUC(0-t)、AUC(0-∞)、MRT(0-t)、VRT(0-t)、cmax差异均有统计学意义(P<0.05)。结论:本研究建立的体内卡铂血药浓度测定方法准确、快速、简便;卡铂药动学参数与剂量相关,AUC=6时卡铂在体循环中的血药浓度更高。

OBJECTIVE： To guide rational drug use and individual therapy with carboplatin. METHODS： HPLC-UV assay was developed. The determination was performed on Kromasil C18 column with mobile phase consisted of H20 at flow rate of 1 ml/ min. The detection wavelength was set at 230 mn and sample size was 50 μl. 10 patients with advanced epithelial ovarian cancer were treated with different doses of carboplatin （AUC=4 or 6） plus pacitaxel, respectively, with 5 patients in each group. Using uridine as internal standard, the plasma concentration of carboplatin was determined to draw C-T curve and calculate pharmacokinet- ic parameters of 2 groups. RESULTS ： The plasma concentration of carboplatin presented a good linear correlation within the range 1.56-100 txg/ml （r=0.999 0）. The relative recovery of carboplatin was 98.91%, RSD=3.96% （n=5）. Pharmacokinetic parameters of carboplatin was calculated after single administration with 2 kinds of drug dosage, and AUC（0-t）, AUC（0-∞）, MRT（0-t）, VRT（0-t）, and Cmax were significantly different between 2 groups （P〈0.05）. CONCLUSIONS： Established method is accurate, rapid and con- venient. The pharmacokinetic parameters of carboplatin are dose-related. Carboplatin get a high plasma concentration in the condi- tion of AUC = 6.