Plasma levels and pharmacokinetics of ethynyl estrogens in various populations: II. Mestranol☆

Abstract A total of 89 adult women from Nigeria, Singapore, Sri Lanka, Thailand and the USA were given single oral doses of mestranol ranging from 50 to 100 μg; the subsequent plasma levels of free mestranol and ethynylestradiol were determined by radioimmunoassay, and certain pharmacokinetic parameters calculated. Mestranol is absorbed very rapidly from the digestive tract and maximum plasma levels are attained in 1–4 hours, the majority at 1–2 hours. Detectable levels of mestranol are present 24 hours postingestion in 58% of subjects after a 50 μg dose and in 79% after a 100 μg dose. At all dose levels, highest plasma mestranol levels and area under the curve of plasma levels (AUC) occurred in Sri Lankan women, and lowest plasma levels in Nigerian women, even when corrected for body surface differences. Plasma levels of ethynylestradiol derived from mestranol rose earlier and reached higher values than those of mestranol itself in every locality. The plasma levels of ethynylestradiol derived from mestranol were lowest and total body clearance highest in the Nigerian group at all dose levels; total body clearance was similar in the other localities. The AUC of plasma levels of ethynylestradiol was compared, by locality, on a dose-for-dose basis for the administration of mestranol or of ethynylestradiol itself. There was no significant difference between the two drugs, except at one dosage level in Thailand. These findings suggest that ethynylestradiol and mestranol are similar in terms of AUC ; a higher peak and a faster decline are observed after administration of the former compound. Substantial differences between localities in the clearance rates of mestranol are suggested; whether these are due to differences in distribution or rate of metabolism or to differences in absorption remains to be determined.