SINGLE-DOSE PHARMACOKINETICS OF SUBLINGUAL VERSUS ORAL-ADMINISTRATIONOF MICRONIZED 17-BETA-ESTRADIOL

Objective: To investigate the pharmacokinetic profiles of different do ses of micronized 17 beta-estradiol administered by oral or sublingual routes. Methods: Single doses of micronized 17 beta-estradiol were ad ministered orally (1 mg, 0.5 mg) or sublingually (1 mg, 0.5 mg, 0.25 m g) to six postmenopausal women in a randomized clinical trial. We calc ulated pharmacokinetic parameters for estradiol (E2) and estrone (E1) of maximum serum concentration, time to maximum serum concentration, t erminal half-life, area under the concentration curve, and oral cleara nce. Serum levels of El sulfate also were compared at 4, 12, and 24 ho urs after dosing. Results: Sublingual administration resulted in rapid absorption with significantly higher E2 levels than did comparable or al dosing. Estrone levels did not vary with route of administration bu t correlated with the dosage administered. Estrone sulfate levels corr elated with the dosage administered and also tended to be higher with sublingual administration. Sublingual administration resulted in a sig nificantly lower E1 to E2 ratio during the 24 hours than did oral admi nistration. Conclusion: Sublingual administration of micronized 17 bet a-estradiol results in a rapid, burst-like absorption into the systemi c circulation, yielding high E2 levels that fall rapidly over the firs t 6 hours. Copyright (C) 1997 by The American College of Obstetricians and Gynecologists.