Normal metabolism of debrisoquine and theophylline in a slow tolbutamide metaboliser

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 threefold 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. (Aust NZ J Med 1985; 15: 348–349.)