Bioavailability and pharmacokinetics of norethisterone in women after oral doses of ethynodiol diacetate.

ABSTRACT

PIP: Bioavailability and pharmacokinetics of norethisterone (NE) were studied in 12 women, aged 21-37 years, after oral doses of ethynodiol diacetate (EDA). Plasma NE levels, measured by radioimmunoassay, were used to compare the bioavailability of EDA tablets (Ovulen 50; 1 mg EDA plus .05 mg ethinyl estradiol) with that of a standard oral solution of EDA. The 3 different batches of tablets studied showed different in vitro dissolution rates, 82.6%, 94.6%, and 99% at 3 hours. No marked differences were seen in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak plasma NE levels were reached within 4 hours of EDA administration in solution or tablets. Following the peak, NE plasma levels declined in 2 phases, with mean terminal elimination 1/2-lives of 4-6.9 hours. These results have shown that small variations in in vitro dissolution rates do not affect the bioavailability of NE from tablets containing EDA.