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Tolbutamide 4‐hydroxylase activity of human liver microsomes: effect of inhibitors.
Author(s) -
Purba HS,
Back DJ,
Orme ML
Publication year - 1987
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1987.tb03167.x
Subject(s) - tolbutamide , microsome , cytochrome p450 , isozyme , cytochrome , hydroxylation , endocrinology , chemistry , enzyme , medicine , metabolism , biochemistry , pharmacology , biology , insulin
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.