| Abstract: | 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. |
