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Dose-Effect Study of Intranasal Administration of Growth Hormone-Releasing Hormone-44-NH2 in Healthy Subjects^*

Centre de Médecine Nucléaire (Y.K., R.C., P.L., C.K., P.C., G.S.) and Service d’ORL Hôpital de la Croix- Rousse (B.N.) and Sanofi Recherche (G.F.) Montpellier, France Lyon, France
Sanofi Recherche (G.F.) Montpellier, France

Address requests for reprints to: Dr. G. Sassolas, Centre de Médecine Nucléaire, 59 boulevard Pinel, Lyon Cedex 3, France.

Intranasal (in) administration of GH-releasing hormone-40- (GHRH-40) has been demonstrated to be efficient in stimulating GH secretion at doses equal to or higher than 30 µg/kg in man. We performed a dose-response study with GHRH-44-NH2 (GHRH) given by nasal spray and closely monitored local tolerance. Twelve normal young men were given 5 GHRH doses (125, 250, 500, 750, and 1000 µg) and placebo in random order according to a latin square design. Mild symptoms of local intolerance, subjective, objective, or both, were noted in the first 20 min after spray in 30 of 72 tests, and a significant difference (P = 0.003) was obtained in their frequency between the group placebo plus the lowest dose and the group of the other doses. The areas under the GH curves were significantly different between the subjects and the doses (by analysis of variance, P = 0.001 and P = 0.025, respectively). Multiple comparison tests showed a significant difference between the 3 highest doses and the placebo (P = 0.005, P = 0.05, and P = 0.02, respectively) and a significant difference between the highest dose and the 2 lowest doses (P = 0.005). By weighted linear regression between GH areas under the curve and GHRH doses the dose-response relationship was established as: y = 1.226x + 457. The magnitude of the GH peaks induced by in GHRH was significantly lower than that induced by iv GHRH.

We conclude that in the normal young men tested, who were high responders to GHRH (as demonstrated by iv test), a 500-µg dose is sufficient to elicit GH secretion. Local tolerance, although imperfect, appears satisfactory to permit a clinical trial in children.

^* This work was supported by a grant from Sanofi Recherche, Montpellier, France.

Received November 1, 1989.