Dose-related suppression of serum luteinizing hormone in women by a potent new gonadotropin-releasing hormone antagonist (Ganirelix) administered by intranasal spray.
OBJECTIVE
To determine if the GnRH antagonist (GnRH-a) Ganirelix (Syntex Research, Palo Alto, CA), administered by intranasal (IN) spray to normal women, is absorbed into the systemic circulation and suppresses LH secretion.


METHODS
A single center, open label, nonrandomized, dose-escalation study.


METHODS
Academic research environment.


METHODS
Normal female volunteers ages 23 to 43 years.


METHODS
Ganirelix was administered as a single dose by IN spray. The administered doses and the number of women receiving each of them were 0.1 mg (n = 1), 0.3 mg (n = 1), 1 mg (n = 2), 3 mg (n = 5), and 6 mg (n = 5). Blood samples were collected from -15 minutes to 24 hours after dosing.


METHODS
Serum concentrations of Ganirelix and LH.


RESULTS
Ganirelix was absorbed rapidly. The mean time to maximal serum levels in the 3- and 6-mg groups was 0.67 and 0.53 hour, respectively. Mean serum LH levels were suppressed by > or = 35% relative to baseline from 2 to 12 hours after dosing in both groups. The mean maximal percent decrease in serum LH was -62% (at 8 hours after dosing) and -74% (at 6 hours after dosing) in the 3- and 6-mg groups, respectively.


CONCLUSIONS
Single dose IN administration of 3 or 6 mg of Ganirelix suppressed serum LH levels in women, further enhancing the potential clinical utility of this potent GnRH-a. This is the first clinical report of a GnRH-a reducing the secretion of a pituitary gonadotropin when administered by an IN delivery system. Based on the duration and extent of LH suppression observed in this study, Ganirelix, administered by twice daily IN spray, may be effective for the treatment of gonadal hormone-dependent disorders in women.
Fujimoto
V Y
VY
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, USA.
Monroe
S E
SE
Nelson
L R
LR
Downey
D
D
Jaffe
R B
RB
D000281:Administration, Intranasal; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood*; D008657:Metabolic Clearance Rate; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; C061018:ganirelix