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 (Syn tex Research, Pale Alto, CA), administered by intranasal (IN) spray to normal women, is absorbed into the systemic circulation and suppresse s LH secretion. Design: A single center, open label, nonrandomized, do se-escalation study. Setting: Academic research environment. Patient(s ): Normal female volunteers ages 23 to 43 years. Intervention(s): Gani relix 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). Bloo d samples were collected from -15 minutes to 24 hours after dosing. Ma in Outcome Measure(s): Serum concentrations of Ganirelix and LH. Resul t(s): Ganirelix was absorbed rapidly. The mean time to maximal serum l evels in the 3- and 6-mg groups was 0.67 and 0.53 hour, respectively. Mean serum LH levels were suppressed by greater than or equal to 35% r elative to baseline from 2 to 12 hours after dosing in both groups. Th e 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. Conclusion(s): 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 fir st clinical report of a GnRH-a reducing the secretion of a pituitary g onadotropin when administered by an IN delivery system. Based on the d uration and extent of LH suppression observed in this study, Ganirelix , administered by twice daily IN spray, may be effective for the treat ment of gonadal hormone-dependent disorders in women.