Schellens J H, Soons P A, van der Wart J H, Hoevers J W, Breimer D D
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
Br J Clin Pharmacol. 1991 Feb;31(2):175-8. doi: 10.1111/j.1365-2125.1991.tb05508.x.
Nifedipine, sparteine and phenytoin were administered orally to eight healthy subjects separately and as a 'cocktail' on four different occasions to investigate any kinetic interactions. All subjects were extensive metabolizers of sparteine. After drug intake plasma and urine samples were collected up to 32 h and the concentrations of parent drugs and main metabolites were measured. Clearances and formation clearances were not significantly different after single substrate and 'cocktail' administration. Low or non significant correlation coefficients were found between the oxidation of the individual substrates or formation of their metabolites. With this strategy of simultaneous administration of substrates ('cocktail') it appears possible to characterize (and correlate) activities of different cytochrome P-450 isoenzymes, without the disturbing influence of intraindividual variation of drug oxidation with time.
将硝苯地平、司巴丁和苯妥英分别口服给予8名健康受试者，并在4个不同场合以“鸡尾酒”形式给药，以研究任何动力学相互作用。所有受试者都是司巴丁的广泛代谢者。药物摄入后，收集血浆和尿液样本长达32小时，并测量母体药物和主要代谢物的浓度。单底物给药和“鸡尾酒”给药后，清除率和生成清除率无显著差异。在各个底物的氧化或其代谢物的生成之间发现低或无显著相关性系数。采用这种同时给予底物（“鸡尾酒”）的策略，似乎有可能表征（并关联）不同细胞色素P-450同工酶的活性，而不受药物氧化随时间的个体内变异的干扰影响。
