Schellens J H, Ghabrial H, van der Wart H H, Bakker E N, Wilkinson G R, Breimer D D
Division of Pharmacology, University of Leiden, The Netherlands.
Clin Pharmacol Ther. 1991 Nov;50(5 Pt 1):520-8. doi: 10.1038/clpt.1991.177.
The effects of quinidine on oxidative routes of drug metabolism mediated by different forms of cytochrome P450 were investigated in 10 healthy subjects. Each subject was studied on three different occasions and separately received oral administration of (1) a "cocktail" of nifedipine (5 mg), sparteine sulfate (90 mg), and mephenytoin (100 mg), (2) quinidine sulfate (200 mg), and (3) quinidine sulfate followed by the "cocktail" 1 hour later. Quinidine pretreatment significantly inhibited the aromatization of nifedipine to its major first-pass pyridine metabolite (M-0) and prolonged the elimination half-life of the calcium channel antagonist, both by about 40%. More marked inhibition of metabolism was observed with sparteine, and the formation of dehydrosparteine was abolished. A significant correlation was found between the 0-8-hour urinary ratio and the plasma concentration ratio of sparteine to dehydrosparteine obtained 4 hours after drug administration. No quinidine-induced changes were observed in the 4-hydroxylation of mephenytoin. The interaction between quinidine and nifedipine supports the involvement of a common P450 (P450IIIA4) in the metabolism of the two drugs.
在10名健康受试者中研究了奎尼丁对由不同形式细胞色素P450介导的药物代谢氧化途径的影响。每名受试者在三种不同情况下接受研究，并分别口服：(1)硝苯地平（5毫克）、硫酸司巴丁（90毫克）和甲妥英（100毫克）的“鸡尾酒”；(2)硫酸奎尼丁（200毫克）；(3)硫酸奎尼丁，1小时后再给予“鸡尾酒”。奎尼丁预处理显著抑制硝苯地平向其主要首过吡啶代谢物（M-0）的芳构化，并使钙通道拮抗剂的消除半衰期延长约40%。观察到司巴丁的代谢抑制更为明显，脱氢司巴丁的形成被消除。给药4小时后获得的司巴丁与脱氢司巴丁的0至8小时尿比值与血浆浓度比值之间存在显著相关性。未观察到奎尼丁诱导的甲妥英4-羟基化变化。奎尼丁与硝苯地平之间的相互作用支持一种共同的细胞色素P450（P450IIIA4）参与这两种药物的代谢。
