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European Journal of Clinical Pharmacology

, Volume 46, Issue 5, pp 421–425 | Cite as

Growth hormone-releasing activity of hexarelin in humans

A dose-response study
  • B. P. Imbimbo
  • T. Mant
  • M. Edwards
  • D. Amin
  • N. Dalton
  • F. Boutignon
  • V. Lenaerts
  • P. Wüthrich
  • R. Deghenghi
Originals

Abstract

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 in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2 ·μg·kg−1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations 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 (Cmax) were 3.9, 26.9, 52.3, 55.0 ng·ml−1 after 0, 0.5, 1 and 2 μg·kg−1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0–180) were 0.135, 1.412, 2.918 and 3.695 μg·min·ml−1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 μg·kg−1 for Cmax and AUC0–180, respectively. The corresponding Emaxs were 55.1 ng·ml−1 and 3936 ng·min·ml−1, thus indicating that the effect after the 2 μg·kg−1 dose is very close to the maximal response. Plasma glucose, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone and insulin-like growth factor I were unaffected by hexarelin administration, while the peptide caused a slight increase in prolactin, cortisol and adrenocorticotropic hormone levels. Hexarelin was well tolerated in all subjects. The results of this study indicate that intravenous administration of hexarelin in man produces a substantial and dose-dependent increase of growth hormone plasma concentrations.

Key words

Hexarelin Growth hormone growth hormone releasing peptides 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • B. P. Imbimbo
    • 1
  • T. Mant
    • 2
  • M. Edwards
    • 2
  • D. Amin
    • 2
  • N. Dalton
    • 2
  • F. Boutignon
    • 3
  • V. Lenaerts
    • 3
  • P. Wüthrich
    • 3
  • R. Deghenghi
    • 3
  1. 1.Medical DepartmentMediolanum FarmaceuticiMilanItaly
  2. 2.Drug Research UnitGuy's HospitalLondonUK
  3. 3.EuropeptidesArgenteuilFrance

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