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2‐Hydroxylation of ethinyloestradiol in relation to the oxidation of sparteine and antipyrine.
Author(s) -
Back DJ,
Maggs JL,
Purba HS,
Newby S,
Park BK
Publication year - 1984
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.1365-2125.1984.tb02511.x
Subject(s) - hydroxylation , metabolite , chemistry , metabolism , sparteine , glucuronide , enzyme , pharmacology , cytochrome p450 , debrisoquine , drug metabolism , biochemistry , stereochemistry , cyp2d6 , medicine
The metabolism of [3H]ethinyloestradiol (EE2) was investigated in six male subjects who had been phenotyped with respect to sparteine metabolism (three metabolizers and three non‐metabolizers). Urinary metabolite profiles of EE2 were virtually identical. Following enzyme hydrolysis of sulphate and glucuronide conjugates the major urinary metabolite was 2‐methoxyEE2. The ratio EE2:2‐methoxyEE2 was taken as a measure of EE2 2‐hydroxylation (metabolizers, 2.4 +/‐ 0.3; non‐ metabolizers, 2.5 +/‐ 0.4). Primaquine (45 mg), previously shown to inhibit antipyrine metabolism, had no effect on EE2 2‐hydroxylation. Supporting studies in rats showed that acute administration of primaquine (50 mg/kg) and 1‐methylimidazole (50 mg/kg) inhibited antipyrine but not EE2 metabolism. It is concluded that the cytochrome P‐450 enzyme responsible for 2‐hydroxylation of EE2 is distinct from the enzymes involved in the oxidation of sparteine and antipyrine.