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 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.
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003647:Debrisoquin / Q000097:blood*; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism; D007546:Isoquinolines / Q000097:blood*; D008297:Male; D013806:Theophylline / Q000097:blood* / Q000652:urine; D014044:Tolbutamide / Q000097:blood*
D007527:Isoenzymes; D007546:Isoquinolines; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D013806:Theophylline; D003647:Debrisoquin