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 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.micrograms.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 micrograms.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 micrograms.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 microgram.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 micrograms.kg-1 dose is very close to the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
Imbimbo
B P
BP
Medical Department, Mediolanum Farmaceutici, Milan, Italy.
Mant
T
T
Edwards
M
M
Amin
D
D
Dalton
N
N
Boutignon
F
F
Lenaerts
V
V
Wüthrich
P
P
Deghenghi
R
R
D000328:Adult; D000595:Amino Acid Sequence; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood*; D006133:Growth Substances / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D006133:Growth Substances; D006728:Hormones; D009842:Oligopeptides; C086184:hexarelin; D013006:Growth Hormone