Bioequivalence of a 17 beta-estradiol hydroxypropyl-beta-cyclodextrin complex in postmenopausal women.
Five postmenopausal women received single doses of a 0.675 mg estradiol hydroxypropyl-beta-cyclodextrin (estradiol-HP beta CD) sublingual tablet by the sublingual and oral route. A single dose of a 1 mg micronized estradiol tablet was given orally for comparison. Blood samples were obtained over 48 hours for measurement of estradiol, estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Sublingual administration produced faster and significantly higher peak estradiol concentrations than after oral administration of either estradiol-HP beta CD or micronized estradiol. The concentration-time area under the curve of estradiol after sublingual estradiol-HP beta CD was also significantly larger than after oral administration of either estradiol-HP beta CD or micronized estradiol, reflecting a larger estradiol bioavailability. The estradiol/estrone concentration ratio after sublingual estradiol-HP beta CD revealed a predominance of estradiol for the first 2 hours after the dose, followed by an estrone predominance. Both oral doses produced a predominant delivery of estrone to the systemic circulation. There was not difference in time-averaged LH suppression between the three phases. However, estradiol-HP beta CD sublingually produced greater FSH suppression than oral micronized estradiol.
Hoon
T J
TJ
Section for Drug Evaluation, College of Medicine, the University of Illinois at Chicago.
Dawood
M Y
MY
Khan-Dawood
F S
FS
Ramos
J
J
Batenhorst
R L
RL
D000286:Administration, Sublingual; D003505:Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D013810:Therapeutic Equivalency; D047392:beta-Cyclodextrins
C085639:17-estradiol hydroxypropylcyclodextrin complex; D003505:Cyclodextrins; D006065:Gonadotropins, Pituitary; D047392:beta-Cyclodextrins; D004970:Estrone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone