Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects.
BACKGROUND
An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572.


OBJECTIVE
Our objective was to establish the pharmacological profile and the GH-releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration.


METHODS
This study was a single-center escalating dose study with oral and ID applications.


METHODS
In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight.


RESULTS
The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers.


CONCLUSIONS
This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration.
Piccoli
Franziska
F
Clinical Research Center, Department of Research, Division of Gastroenterology, University Hospital, CH-4031 Basel, Switzerland.
Degen
Lukas
L
MacLean
Carol
C
Peter
Shajan
S
Baselgia
Luisa
L
Larsen
Finn
F
Beglinger
Christoph
C
Drewe
Jürgen
J
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone; D006207:Half-Life; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007211:Indoles; D007441:Intubation, Gastrointestinal; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D036361:Peptide Hormones / Q000819:agonists*; D014364:Tryptophan / Q000031:analogs & derivatives
D054439:Ghrelin; D006728:Hormones; D007211:Indoles; D009842:Oligopeptides; D036361:Peptide Hormones; D019382:Human Growth Hormone; C582727:macimorelin; D014364:Tryptophan; D013007:Growth Hormone-Releasing Hormone