An investigation of the pharmacokinetics of ethynylestradiol in women using radioimmunoassay

Abstract

A radioimmunoassay for ethynylestradiol (EE) which is applicable to plasma samples obtained from women, who have taken a combination type oral contraceptive, has been developed and fully validated. Plasma concentration of EE rise to a peak of 128 pg/ml following the oral administration of 50 microgram EE. Following the intravenous administration of the same dose of EE, plasma concentrations of the steroid declined biexponentially, the two half-lives being 0.83 and 6.75 hours. Comparison of the results of the intravenous and oral administration of the steroid suggested that its oral bioavailability is 42%. Although EE thus has a lower bioavailability than norethindrone, the pharmacokinetics of the two steroids, as reflected by half-lives, plasma clearance and volume of distribution, are very similar. The occurrence of a secondary peak in plasma at around 12 hours after dosing gave strong evidence that EE undergoes enterohepatic circulation in women; an event that may have considerable clinical significance.

PIP: A radioimmunoassay for ethinyl estradiol (EE) was developed and fully evaluated. It is applicable to plasma samples obtained after administration of oral contraceptives containing norethindrone or norgestrel in addition to EE. In addition, the bioavailability of EE, by comparison of its pharmacokinetics after intravenous and oral ingestion, was determined. Plasma concentrations of EE rose to a peak of 128 pg/ml after oral doses of 50 mcg of EE. After the intravenous administration of 50 mcg of EE, plasma levels of the steroid declined biexponentially; respective half-lives for the 2 routes were .83 and 6.75 hours. By comparing these route-of-administration results, the bioavailability of EE was determined to be 42%. EE thus has a lower bioavailability than norethindrone, yet the pharmacokinetics of the 2 steroids, including half-lives, plasma clearance, and volume of distribution, were similar. A secondary peak occurred in plasma at about 12 hours after dosing, giving strong evidence that EE undergoes enterohepatic circulation in women, an event of considerable clinical significance. The most distinctive feature of the radioimmunoassay used in this study is the use of partition between methanol/water and petroleum ether to remove excess fats from the initial ether extract. The inter- and intraassay precision of this newly developed method were within the range that is normally expected of such an assay.