2-Hydroxylation of ethinyloestradiol in relation to the oxidation of sparteine and antipyrine.

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.