GROWTH HORMONE-RELEASING ACTIVITY OF HEXARELIN IN HUMANS - A DOSE-RESPONSE STUDY

Hexarelin is a new hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D -Phe-Lys- NH2) that stimulates the release of growth hormone both in vitro and i n vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healt hy human subjects. Twelve adult male volunteers received single intrav enous boluses of 0.5, 1 and 2.mu g.kg(-1) hexarelin as well as placebo . For safety, drug doses were given in a rising-dose fashion with plac ebo randomly inserted into the sequence. Plasma growth hormone concent rations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (C-max) were 3.9, 26.9, 52.3, 55.0 ng.ml(-1) a fter 0, 0.5, 1 and 2 mu g.kg(-1), respectively. The corresponding area s under the curve of growth hormone plasma levels from drug injection to 180 min (AUC(0-180)) were 0.135, 1.412, 2.918 and 3.695 mu g.min.ml (-3). The theoretical maximum response (E(max)) and the dose that prod uces half of the maximum response (ED(50)) were estimated using logist ic regression. The calculated ED(50) values were 0.50 and 0.64 mu g.kg (-1) for C-max and AUC(0-180), respectively. The corresponding E(max)s were 55.1 ng.ml(-1) and 3936 ng.min.ml(-1), thus indicating that the effect after the 2 mu g.kg(-1) dose is very close to the maximal respo nse. Plasma glucose, luteinising hormone, follicle-stimulating hormone , thyroid-stimulating hormone and insulin-like growth factor I were un affected by hexarelin administration, while the peptide caused a sligh t increase in prolactin, cortisol and adrenocorticotropic hormone leve ls. Hexarelin was well tolerated in all subjects. The results of this study indicate that intravenous administration of hexarelin in man pro duces a substantial and dose-dependent increase of growth hormone plas ma concentrations.