多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

目的 探讨多剂量复方苦参注射液与盐酸吉西他滨联合使用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 选取24只健康雄性SD大鼠，随机分为对照组和实验组（复方苦参高、中、低3个剂量组），实验组大鼠连续10 d尾静脉给予不同剂量的复方苦参注射液，对照组大鼠连续10 d尾静脉给予等量的生理盐水，于最后一天给药5 min后注射吉西他滨，分别于13个时间点眼底静脉丛采血，通过高效液相色谱法测定血样中吉西他滨的浓度，并采用DAS 2.0软件处理，得出吉西他滨药物代谢动力学参数。结果 各组大鼠体内吉西他滨药物代谢动力学过程符合二室模型拟合；与对照组比较，复方苦参高剂量组可以增加吉西他滨的药-时曲线下面积（P<0.05），并延长平均滞留时间（P<0.05）。结论 多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有明显影响，在临床上应根据病情需要联合使用复方苦参注射液与吉西他滨。

Effect of Multiple-dose Compound Kushen Injection on Pharmacokinetic Parameters of Gemcitabine in Rats

Objective To investigate the effect of multiple-dose Compound Kushen Injection (CKI) on the pharmacokinetic parameters of gemcitabine in rats after the combined use of CKI and gemcitabine hydrochloride. Methods A total of 24 healthy male Sprague-Dawley rats were randomly divided into control group and experimental group, and the experimental group was further divided into high-, middle-, and low-dose CKI groups. The rats in the experimental group were given different doses of CKI via the caudal vein for 10 consecutive days, and those in the control group were given an equal volume of normal saline via the caudal vein for 10 consecutive days. Gemcitabine was injected at 5 minutes after administration on the last day. Blood samples were collected from the fundus venous plexus at 13 time points to measure the concentration of gemcitabine by high-performance liquid chromatography. DAS 2.0 software was used to obtain the pharmacokinetic parameters of gemcitabine. Results The pharmacokinetic process of gemcitabine in each group was consistent with the two-compartment model. Compared with the control group, the high-dose CKI group had a significant increase in the area under the plasma concentration-time curve of gemcitabine (P<0.05) and a significantly longer mean residence time of gemcitabine (P<0.05). Conclusion Multiple-dose CKI has a great impact on the pharmacokinetics of gemcitabine in rats, and the combination of CKI and gemcitabine should be used based on patient conditions in clinical practice.