Investigations of pharmacokinetics of ethinyloestradiol to specific consideration of a possible first-pass effect in women

Abstract

Ethinyloestradiol-3H was given intravenously and orally to four and three women, respectively, in a dose of 60 micrograms and 3 mg. To another three female volunteers, 100 micrograms of ethinyloestradiol was administered by both routes in succession. Drug concentration in plasma and total radioactivity in plasma, urine and faeces were measured for different periods of time. Intraindividual comparison of the area under the drug level vs. time curve after intravenous and oral administration of 100 micrograms showed that ethinyloestradiol is subject to an about 60% first-pass effect in women. The time course of ethinyloestradiol concentration in plasma can be described by a 3-compartment model after intravenous injection and by a 2-compartment model after oral administration, because an early disposition phase with a half-life of about 15 minutes only becomes visible after i.v. injection. On an average, the terminal half-life of unchanged ethinyloestradiol level and total radioactivity was calculated to be about 1 day. However, a high variability was found with this parameter as well as with the rate and degree of elimination in urine.

PIP: Investigations of pharmacokinetics of ethinyl estradiol (EE) to specific consideration of a possible 1st-pass effect in women are reported. Tritiated EE was given intravenously and orally to 4 and 3 women, respectively, in a dose of 60 mcg and 3 mg. 3 female volunteers received 100 mcg of EE by both routes in succession. EE concentration in plasma and total radioactivity in plasma, urine, and feces were measured for different periods of time. Intraindividual comparison of the area under the drug level vs time curve following iv and oral administration of 100 mcg showed that EE is subject to about 60% 1st-pass effect in women. The time course of EE concentration in plasma can be described by a 3-compartment model after iv injection and by a 2-compartment model after oral administration, because an early disposition phase with a 1/2-life of about 15 only became visible after iv injection. The terminal 1/2-life of unchanged EE level and total radioactivity was calculated to be about 1 day.