Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects.
OBJECTIVE
It has been demonstrated that ghrelin plays a major role in the regulation of GH secretion and food intake. These actions make ghrelin a strong candidate for the treatment of GH deficiency, anorexia and cachexia. However, only preliminary studies have been performed to assess ghrelin administration in humans. In this study, we have conducted a double-blind, randomized, placebo-controlled trial to investigate the pharmacokinetics, safety, and endocrine and appetite effects of ghrelin in young healthy volunteers.


METHODS
Eighteen male volunteers were randomly assigned into three groups of six subjects: low- and high-dose ghrelin groups, who received intravenous injections of 1 and 5 microg/kg ghrelin (acylated form) respectively, and a placebo group who were injected with mannitol instead of ghrelin.


RESULTS
Acylated ghrelin disappeared more rapidly from plasma than total ghrelin, with elimination half life (t(1/2)) of 9-13 and 27-31 min respectively. The number of subjects that experienced adverse effects did not significantly differ among the three groups, and all adverse effects were transient and well tolerated. Both the low and high doses of ghrelin strongly stimulated GH release (peak plasma concentration (C(max,0-90 min)): 124.2+/-63.9 and 153.2+/-52.2 ng/ml for 1 and 5 microg/kg ghrelin respectively). Slight alterations of blood glucose and insulin levels after the injection were observed. Although not statistically significant, ghrelin administration tended to increase hunger sensation in a dose-dependent manner.


CONCLUSIONS
These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.
Akamizu
Takashi
T
Ghrelin Research Project, Department of Experimnetal Therapeutics, Kyoto University Hospital, Kyoto University School of Medicine, Kyoto 606-8507, Japan.
Takaya
Kazuhiko
K
Irako
Taiga
T
Hosoda
Hiroshi
H
Teramukai
Satoshi
S
Matsuyama
Akiko
A
Tada
Harue
H
Miura
Kazumi
K
Shimizu
Akira
A
Fukushima
Masanori
M
Yokode
Masayuki
M
Tanaka
Koichi
K
Kangawa
Kenji
K
D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001786:Blood Glucose; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D054439:Ghrelin; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D036361:Peptide Hormones / Q000009:adverse effects / Q000493:pharmacokinetics*
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I