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目的建立HPLC测定大鼠血浆中伊马替尼及其代谢产物GCP74588的浓度,并研究不同浓度复方苦参素注射液对伊马替尼及其代谢产物的药动学的影响。方法将SD大鼠按体质量均衡原则分成复方苦参注射液低、中、高剂量[0.1,0.2,0.4 m L·(100 g)~(-1),i.p.]组和正常对照组,每组6只,复方苦参注射液连续给药9 d,第10天给予30 mg·kg~(-1)甲磺酸伊马替尼灌胃,按时间点采集血样处理并检测。结果低剂量诱导对伊马替尼及CGP74588均无明显影响;中剂量诱导使伊马替尼的C_(max)降低39.68%、CLz/F增加了62.96%、AUC(0-∞)减少35.70%,而对其代谢产物CGP74588无明显影响;高剂量诱导使伊马替尼C_(max)降低49.04%、Vz/F增加了1.04倍,CLz/F增加了48.15%、AUC(0-t)减少了33.23%、AUC_(0-∞)减少了28.96%,MRT(0-∞)增加了47.31%,而其代谢产物CGP74588的C_(max)降低45.15%,CLz/F增加75.29%,AUC(0-∞)降低33.95%、MRT_(0-t)增加18.53%。结论苦参诱导肝脏CYP3A与P-gp使伊马替尼血浆中浓度降低,有可能会导致治疗失败,所以临床医师在使用时应尽量避免合用这2种药物,或者在监测伊马替尼的浓度下使用。
OBJECTIVE To establish a HPLC method for the determination of imatinib and its metabolite GCP74588 in rat plasma and to study the effects of different concentrations of oxymatrine injection on the pharmacokinetics of imatinib and its metabolites. Methods SD rats were divided into two groups according to body mass balance: low, medium and high doses of Compound Kushen Injection [0.1,0.2,0.4 m L · (100 g) -1, ip] and normal control group Group 6, compound Kushen injection for 9 d, on the 10th day given 30 mg · kg -1 imatinib mesylate gavage, blood samples were collected and tested at time points. Results Low dose induction had no significant effect on imatinib and CGP74588. Cmax of imatinib decreased by 39.68%, CLz / F increased by 62.96%, and AUC (0-∞) decreased by 35.70% , While its metabolite CGP74588 had no significant effect. High dose induced a decrease of 54.04% in Imax, 1.04 times in Vz / F, 48.15% in CLz / F and a decrease in AUC (0-t) (C-max) decreased 45.15%, CLz / F increased 75.29%, AUC (0-∞) decreased by 33.23%, AUC_ (0-∞) decreased by 28.96%, MRT (0-∞) increased by 47.31% -∞) decreased by 33.95%, MRT_ (0-t) increased by 18.53%. Conclusion Sophora flavescens induced liver CYP3A and P-gp reduce the concentration of imatinib plasma may lead to treatment failure, so clinicians should be avoided in the use of these two drugs in combination, or in the monitoring of imatinib Concentration use.