药根碱药物相互作用及其机制研究

目的　研究药根碱 (Jat)与华法令 (War)、硫喷妥钠(Thi)、甲苯磺丁脲 (D86 0 )合用时对药物效应的影响及其机制。方法　①以药效学方法观察Jat与War合用对小鼠凝血时间的影响 ;②观察Jat与Thi合用对小鼠睡眠时间的影响 ;③观察Jat与甲苯磺丁脲合用时 ,对小鼠血糖的影响 ;④根据荧光静态猝灭理论 ,采用荧光法测定Jat与人血清白蛋白的结合常数。结果　①Jat与War合用 ,小鼠凝血时间延长 (P <0 0 1)。①Jat与Thi合用 ,能延长小鼠睡眠时间 (P<0 0 5)。③Jat与甲苯磺丁脲合用时能降低小鼠血糖水平(P <0 0 1)。④荧光法测得Jat与人血清白蛋白的结合常数为 1 2 9× 10 4 L·mol- 1,结合常数大 ,表明二者有高度的结合。结论　Jat与War、Thi、甲苯磺丁脲合用 ,可使其药效(或毒性 )增强 ,导致药物相互作用。其可能的机制是Jat竞争血浆蛋白结合部位 ,使其游离药物浓度增高 ,药效 (或毒性 )增强

Study on the interactions between jatrorrhizine and other drugs and mechanisms of the interaction

AIM To study the interactions between jatrorr hi zine(Jat) and warfarin(War),thiopental(Thi) or tolbutamide(D 860 ) and mecha nisms of the interaction. METHODS ①By the slide method, effect of Jat on coagulation time of the mice administrated War was observed; ②By rig ht reflex method, effect of Jat on sleep time of the mice administrated Thi was obser ved; ③Determining level of blood glucose of the mice, effect of Jat on action o f D 860 was observed; ④By fluorescence method, the fluorescence quenching of human serum albumin(HSA) by its interaction with Jat, the interaction dissoc iation constant of HSA and Jat from a double recipro cal Lineweaver-Burk plot was determined. RESULTS ①Jat can prolo ng coagulation time of the mice po War(P<0 01). ②Jat can prolong sleep ti me of the mice ip Thi(P<0 05). ③Jat can decrease the level of blood gluco se of the mice po D 860 (P<0 01; vs D 860 +NS group). ④The i nteraction dissociation constants of Jat and human serum albumin was 7 74×10 -5 mol·L -1 . CONCLUSION There were the interactions between Jat and War, Thi or D 860 . Mechanisms of the interaction may be attributed to Jat binding with HSA, dec reasing the binding of War,Thi or D 860 , increasing the blood level of free drug of them, enhanling their actions or toxicity. The binding m ay be a noncompetitive binding with HSA in other sites, producing a chemical cha nge, decreasing the binding of War,Thi or D 860 .