Mihaly G W, Scott H, Hyman M K, Morgan D J, Smallwood R A
Department of Medicine, University of Melbourne, Repatriation Hospital, Victoria, Australia.
J Pharm Pharmacol. 1993 Mar;45(3):215-7. doi: 10.1111/j.2042-7158.1993.tb05535.x.
We have examined the disposition of the cinchona alkaloids quinine and quinidine in the rat recirculating isolated perfused liver preparation. When administered as separate 1 mg doses, the hepatic clearances of quinine and quinidine were similar to the hepatic perfusate rate of 10 mL min-1. When 1 mg of each was administered simultaneously, mean hepatic clearance of quinine was unchanged (9.00 +/- 2.20 mL min-1 separate dosage, n = 7; 6.87 +/- 1.77 mL min-1 simultaneous dosage, n = 7; P > 0.05). By contrast, mean hepatic clearance of quinidine was reduced significantly by concomitant quinine (10.6 +/- 1.72 mL min-1 separate dosage, n = 7; 4.82 +/- 1.25 mL min-1 simultaneous dosage, n = 7; P < 0.05). There was no significant difference in volumes of distribution when each alkaloid was administered separately (131 +/- 46 mL quinine, 129 +/- 21 mL quinidine; P > 0.05) but concomitant quinine administration increased quinidine volume of distribution to 169 +/- 30 mL (P < 0.05). Four further experiments with simultaneous dosages of 0.5 mg of each alkaloid produced similar findings, indicating that the interactions did not derive from nonlinear drug disposition.
我们研究了金鸡纳生物碱奎宁和奎尼丁在大鼠离体肝脏再循环灌注制备模型中的处置情况。当分别给予1mg剂量时，奎宁和奎尼丁的肝脏清除率与肝脏灌注速率10 mL min-1相似。当同时给予每种生物碱1mg时，奎宁的平均肝脏清除率未发生变化（单独给药时为9.00±2.20 mL min-1，n = 7；同时给药时为6.87±1.77 mL min-1，n = 7；P>0.05）。相比之下，奎尼丁的平均肝脏清除率因同时给予奎宁而显著降低（单独给药时为10.6±1.72 mL min-1，n = 7；同时给药时为4.82±1.25 mL min-1，n = 7；P<0.05）。当分别给予每种生物碱时，分布容积没有显著差异（奎宁为131±46 mL，奎尼丁为129±21 mL；P>0.05），但同时给予奎宁会使奎尼丁的分布容积增加到169±30 mL（P<0.05）。另外四项同时给予每种生物碱0.5mg的实验也得到了类似的结果，表明这种相互作用并非源于非线性药物处置。
