摘要
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 )
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 .
出处
《中国药理学通报》
CAS
CSCD
北大核心
2003年第12期1413-1416,共4页
Chinese Pharmacological Bulletin
基金
广东省中医药管理局科研项目No 984 0 3
