伊马替尼与金匮金肾气丸在人工胃/肠液中的相互作用研究

Study on the Interaction Between Imatinib and Jinguishenqi Pill in Simulated Gastric/Intestinal Fluid

伊马替尼为TKI制剂,在白血病及多种肿瘤治疗中具有显著疗效,但是男性患者长期服用后可引起生殖毒性。本课题组前期实验表明金匮金肾气丸可以降低雄性小鼠长期服用伊马替尼引起的生殖毒性。为了便于指导临床合理用药,本实验以高效液相色谱-紫外法(HPLC-UV)测定10.00 mg伊马替尼与不同剂量金匮肾气丸联合使用,在人工胃/肠液中孵育不同时间后,伊马替尼与金匮金肾气丸中三个主要成分含量,进一步研究伊马替尼与金匮金肾气丸的药物相互作用。结果发现:金匮金肾气丸中丹皮酚不受药物间相互作用影响;金匮金肾气丸为3.6 g时伊马替尼含量显著降低(P<0.01),低剂量时不受影响;低于1.2 g剂量时金匮金肾气丸中莫诺苷与伊马替尼不产生相互影响,高于2.4 g时,伊马替尼影响莫诺苷的含量;马钱苷受伊马替尼影响较大,不同剂量联合药物中马钱苷含量均较金匮金肾气丸中含量显著降低(P<0.05),这可能是伊马替尼与金匮金肾气丸相互作用抑制了其溶出。因此伊马替尼和金匮金肾气丸同时服用可能会引起药物间相互作用而降低疗效,推荐间隔2 h以上服用可以达到存效减毒目的。

Imatinib is tyrosine kinase inhibitors(TKI)preparation,which has a significant effect in the treatment of leukemia and many kinds of tumors.However,long-term use of TKI preparation in men will cause reproductive toxicity.The previous experiments showed that Jingui shenqi Pill(JG)could reduce the reproductive toxicity induced by imatinib.In order to further study the interaction between imatinib and JG,and provide guidance for rational clinical drug use,HPLC-UV was used to determine the content of the three main components of imatinib and JG in simulated gastric/intestinal fluid at different time points,after a combined use of 10.00 mg imatinib and different doses of JG.The results showed that paeonol in JP was not affected by drug interaction.The content of imatinib decreased significantly when the dose of JG was 3.6 g(P<0.01),while it was not affected at low doses.Morningside and imatinib did not interact with each other when the dose was lower than 1.2 g,and imatinib affected the content of morroniside when the dose was higher than 2.4 g.Imatinib showed significant effect on loganin,and the content of loganin in different doses of combined drugs was significantly lower than that in JG.This may be caused by the interaction between imatinib and JG which inhibited its dissolution.Therefore,the combination of imatinib and JG may lead to drug interaction and reduce the efficacy.It is recommended to take imatinib at an interval of more than two hours to achieve the purpose of keeping effective and reducing drug toxicity.