Jun 1, 1985

Comparison of the subcutaneous and intranasal administration of an LH-RH antagonist ([N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LH-RH) in the rhesus monkey

Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception
R H AschA V Schally


Although luteinizing hormone-releasing hormone (LH-RH) agonists have been administered successfully by other than systemic routes (oral, intranasal (i.n.) and vaginal), there is no evidence that inhibitory analogues may be used in any form other than injectable. In the present study, we compared the effect of two routes of administration: subcutaneous (s.c.), 0.5, 0.2 and 1 mg; and i.n., 0.2, 1 and 5 mg of an LH-RH antagonist, ORG 30276 ([N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LH-RH) on gonadotropin levels in oophorectomized monkeys. One hour after s.c. administration, FSH and LH values exhibited a dose-dependent fall that lasted for up to 12 h. After s.c. administration, the maximum inhibition of serum FSH and LH was 29 and 41% (0.2 mg dose) and 41 and 58% (1 mg dose), respectively. After i.n. administration, maximum inhibition of serum FSH and LH was 19 and 40% (1 mg) and 32 and 53% (5 mg), respectively. These decreases were dose-related and lasted for up to 12 h. Analysis of the data revealed that the bioavailability of the i.n. route versus the s.c. route ranged from 16 to 26%. This high effectiveness of the i.n. route in terms of bioavailability is markedly greater than that previously reported for LH-RH agonists (1%) a...Continue Reading

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Mentioned in this Paper

Rh-Null, Regulator Type
Recombinant Gonadotropin
Precocious Puberty
Subcutaneous Injections
Antagonist Muscle Action
Gonadotropin [EPC]
Parenteral Route of Drug Administration

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