单剂量复方苦参注射液对吉西他滨在大鼠体内药物代谢动力学参数的影响

摘要

Objective To investigate the influence of combined administration of single-dose Compound Kushen Injection (CKI) and gemcitabine hydrochloride for injection on the pharmacokinetic parameters of gemcitabine in rats.Methods A total of 24 healthy Sprague-Dawley (SD) rats (12 male and 12 female rats) were randomly divided into control group and high-,middle-,and low-dose CKI groups.Blood samples were collected at the orbit at 13 time points,and high-performance liquid chromatography was used to measure the concentration of gemcitabine in blood samples.DAS 3.0 software was used to calculate pharmacokinetic parameters.Results The pharmacokinetic process of intravenously injected gemcitabine in SD rats was fitted to the two-compartment model.There were no significant differences between single and combined administration in distribution half-life time (t1/2α),elimination half-life time (t1/2β),clearance,and area under the plasma concentration-time curve (AUC).Conclusion Single-dose CKI has no significant effect on the pharmacokinetie parameters of gemcitabine in rats,suggesting that single-dose CKI can be combined with gemcitabine hydrochloride for injection in clinical practice.%目的 探讨单剂量复方苦参注射液与注射用盐酸吉西他滨联合用药后对吉西他滨在大鼠体内药物代谢动力学参数的影响.方法 24只健康SD大鼠,雌雄各半,随机分为对照组和复方苦参注射液高、中、低3个剂量组.4组大鼠均在相同13个时间点眼眶采血,采用高效液相色谱法测定血样中吉西他滨的浓度,借助DAS 3.0软件计算药物代谢动力学参数.结果 静脉注射吉西他滨在SD大鼠体内药物代谢动力学过程符合二室模型拟合,在单用和复合给药时分布半衰期(t1/2α)、消除半衰期(t1/2β)、总体消除率(clearance,CL)、药-时曲线下面积(area under curve,AUC)等主要药物代谢动力学参数比较,差异均无统计学意义.结论 单剂量复方苦参注射液对大鼠体内吉西他滨的药物代谢动力学行为无明显影响,在临床上单剂量复方苦参可以与注射用盐酸吉西他滨联合用药.