Normal metabolism of debrisoquine and theophylline in a slow tolbutamide metaboliser

Aust N Z J Med. 1985 Jun;15(3):348-9. doi: 10.1111/j.1445-5994.1985.tb04052.x.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism
  • Debrisoquin / blood*
  • Humans
  • Hydroxylation
  • Isoenzymes / metabolism
  • Isoquinolines / blood*
  • Male
  • Theophylline / blood*
  • Theophylline / urine
  • Tolbutamide / blood*

Substances

  • Isoenzymes
  • Isoquinolines
  • Cytochrome P-450 Enzyme System
  • Tolbutamide
  • Theophylline
  • Debrisoquin