Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: absorption by various routes and absorption enhancement

• Published in: Journal of pharmaceutical sciences Vol. 71; no. 12; p. 1367
• Main Authors: Okada, H, Yamazaki, I, Ogawa, Y, Hirai, S, Yashiki, T, Mima, H
• Format: Journal Article
• Language: English
• Published: United States 01.12.1982
• Subjects: Absorption; Administration, Oral; Aerosols; Animals; Evans Blue; Female; Gels; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - metabolism; Gonadotropin-Releasing Hormone - pharmacology; Leuprolide; Mucous Membrane - metabolism; Ovulation - drug effects; Rats; Rats, Inbred Strains; Tablets; Vagina - metabolism
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600711214

The absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) through different routes was evaluated by determining the ovulation-inducing activity in diestrous rats. Vaginal administration showed the greatest potency among nonparenteral routes and was followed successively by rectal, nasal, and oral administration. Mixed micellar solution with monoolein-bile acids improved the intestinal absorption of leuprolide, and nasal absorption was enhanced by adding sodium glycocholate, surfactin, or polyoxyethylene 9 lauryl ether, but these bioavailabilities were still insufficient. The vaginal absorption was enhanced by organic acids: citric, succinic, tartaric, and glycocholic; the absolute bioavailability increased to approximately 20%. The vaginal absorption from jellies, as practical dosage forms, yielded sufficient activity of leuprolide, but absorption was slightly reduced with highly polar polymers or with higher concentrations of polymers. It was concluded that vaginal administration of leuprolide can be a rational dosage method for a long-term antitumor therapy.