Miners J O, Wing L M, Birkett D J
Aust N Z J Med. 1985 Jun;15(3):348-9. doi: 10.1111/j.1445-5994.1985.tb04052.x.
The metabolism of debrisoquine and theophylline has been studied in a healthy male who was identified as a slow hydroxylator of tolbutamide. Tolbutamide clearance in this subject was three-fold lower than the lowest tolbutamide clearance observed in other healthy males and the drug's half-life was approximately three-fold longer. Despite this, his ability to 4-hydroxylate debrisoquine and both N-demethylate and 8-hydroxylate theophylline was normal. Along with previously published information the data from this subject suggest that tolbutamide hydroxylation, debrisoquine hydroxylation, theophylline N-demethylation, and theophylline 8-hydroxylation involve four distinct isozymes of cytochrome P-450. Furthermore, this report illustrates the difficulties of using the metabolic clearance of a model drug to predict the ability of an individual to clear a range of metabolised drugs.
在一名被确定为甲苯磺丁脲慢羟基化者的健康男性身上，对异喹胍和茶碱的代谢进行了研究。该受试者体内甲苯磺丁脲的清除率比其他健康男性中观察到的最低甲苯磺丁脲清除率低三倍，且药物半衰期约长三倍。尽管如此，他对异喹胍进行4-羟基化以及对茶碱进行N-去甲基化和8-羟基化的能力正常。结合此前发表的信息，该受试者的数据表明，甲苯磺丁脲羟基化、异喹胍羟基化、茶碱N-去甲基化和茶碱8-羟基化涉及细胞色素P-450的四种不同同工酶。此外，本报告说明了使用模型药物的代谢清除率来预测个体清除一系列代谢药物能力的困难。
