PHARMACOKINETICS OF GROWTH HORMONE-RELEASING HORMONE(1-29)-NH2 AND STIMULATION OF GROWTH-HORMONE SECRETION IN HEALTHY-SUBJECTS AFTER INTRAVENOUS OR INTRANASAL ADMINISTRATION

The growth hormone-releasing hormone analogue GHRH(1-29)-NH2 was admin istered intravenously or intranasally to 30 healthy men aged 19-43 yea rs. Intravenous injection of the lowest dose tested, 0.25 mug/kg body weight, elicited significant release of growth hormone (GH). Maximal r elease (mean GH peaks of about 90 mU/l) was obtained with a dose of 1- 2 mug/kg. Although GHRH(1-29)-NH2 was rapidly eliminated after intrave nous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1-29)-NH2 through the nasal mucosa was found to be low, and th e bioavailability was only 3-5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1-29)-NH2, with the maxima l response obtained with about 50 mug/kg; this dose was approximately as potent as 1 mug/kg injected intravenously. The GH response after re peated intranasal administration of GHRH(1-29)-NH2, was sustained: the re was no suppression of GH secretion during the night following a day when GHRH(1-29)-NH2 had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administrati on compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.