The pharmacokinetics of a large (3 mg) oral dose of ethynylestradiol in women.

Plasma levels of ethynylestradiol (EE), EE sulphate (EES), EE glucuronide (EEG) and prolactin were measured in women up to 72 h following the oral administration of 3 mg of EE. The decline in plasma EE levels showed a sharp discontinuity at 10 h which is assumed to be due to the beginning of enterohepatic circulation (EHC). After this event, an apparently terminal monoexponential decline was eventually established with a half-life of 13.1 h. As a result of EHC, the volume of distribution was increased by 60% to 6.0 1.Kg-1 but it does not appear that any significant accumulation of EE would occur during multiple dosing. Plasma levels of EES were, on average, 22.5 times greater than those of EE and this circulating metabolite may act as a reservoir of EE. No circulating EEG could be detected. Comparing these results with those previously obtained with 50 microgram EE, there was no evidence of dose dependency in the pharmacokinetics of this steroid. Plasma prolactin levels were markedly enhanced by this single dose of oestrogen.