Tolbutamide 4-hydroxylase activity of human liver microsomes: effect of inhibitors

Br J Clin Pharmacol. 1987 Aug;24(2):230-4. doi: 10.1111/j.1365-2125.1987.tb03167.x.


Eight samples of human liver have been characterised for microsomal protein content, cytochrome P-450 content, tolbutamide 4-hydroxylase and ethinyloestradiol 2-hydroxylase activities. Cytochrome P-450 content correlated significantly with ethinyloestradiol 2-hydroxylase activity but not with tolbutamide 4-hydroxylase activity. There was no significant correlation between ethinyloestradiol 2-hydroxylase and tolbutamide 4-hydroxylase activities. The maximum tolbutamide 4-hydroxylase activity was 0.45 nmol min-1 mg-1 microsomal protein, with a Km value of 74 microM. A number of compounds were tested for their ability to inhibit tolbutamide metabolism. All the compounds showing inhibition were either non-competitive or mixed non-competitive inhibitors of tolbutamide 4-hydroxylation. These studies suggest that tolbutamide is metabolised by an isozyme of cytochrome P-450 which appears to be distinct from those isozymes metabolising many other drugs.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cytochrome P-450 CYP1A1*
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Kinetics
  • Male
  • Microsomes, Liver / enzymology*
  • Middle Aged
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Mixed Function Oxygenases / metabolism*
  • Proteins / metabolism
  • Steroid Hydroxylases / antagonists & inhibitors
  • Steroid Hydroxylases / metabolism
  • Tolbutamide / metabolism*


  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Proteins
  • Cytochrome P-450 Enzyme System
  • Tolbutamide
  • Mixed Function Oxygenases
  • Steroid Hydroxylases
  • Cytochrome P-450 CYP1A1
  • estrogen 2-hydroxylase
  • tolbutamide 4-hydroxylase