探讨接受BSA指导用药剂量的乳腺癌化疗患者个体间多西他赛药代动力学差异

Investigation of inter-individual docetaxel pharmacokinetic variability in breast cancer patients receiving BSA-based dosing administration with a rapid immunoassay

目的:探索乳腺癌患者接受体表面积(BSA)指导用药剂量的多西他赛(DTX)化疗后患者体内药代动力学多态性,以揭示患者体内药物暴露的差异。方法:采用纳米增强免疫比浊法测定258例患者血浆中的DTX浓度,计算每位患者的关键药代动力学参数AUC,并进行DTX药物浓度监测。结果:258例患者个体间的AUC值分布在0.40~2.67 mg·h/L,变异系数40.6%。采用不同化疗方案的各组患者的AUC并未显示出显著的差异,<50岁以及50~70岁组患者的AUC显著低于>70岁组患者的AUC(P=0.007,P=0.012)。结论:采用BSA指导用药剂量的DTX化疗可导致个体患者间的疗效和毒副作用出现巨大差异,需优化现有的用药剂量制定方案以提高乳腺癌患者尤其是老年乳腺癌患者(>70岁)DTX药物有效性并降低毒副作用。

Objective:To investigate the pharmacokinetic variety of breast cancer patients receiving body surface area(BSA)based docetaxel(DTX)dosing chemotherapy,to reveal the difference of inter-individual drug exposure.Methods:Plasma DTX concentration was measured with nano-particle-enhanced immune turbidimetry.The key pharmacokinetic parameter area under curve(AUC)was calculated with NLME mathematical software via Bayesian analysis for drug monitoring.Results:AUCs of 258 patients ranged from 0.40 to 2.67 mg·h/L,the coefficient of variance was 40.6%.AUCs showed no significant difference in patients receiving different chemotherapeutical regimens.However,the AUCs of<50 years old group and 50~70 years old group were significant lower than that of>70 years old group.Conclusion:BSA based dosing may cause significant difference in efficacy and toxicity effect in breast cancer patients receiving DTX chemotherapy.Optimized drug dosing method is in urgent need to improve the efficacy and minimize the toxicity effect for breast cancer patients,especially>70 years old patients,receiving DTX chemotherapy.