title: Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects.
abstract: 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.
authors.affiliation: Clinical Research Center, Department of Research, Division of Gastroenterology, University Hospital, CH-4031 Basel, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Piccoli
authors.forename: Lukas
authors.initials: L
authors.lastname: Degen
authors.forename: Carol
authors.initials: C
authors.lastname: MacLean
authors.forename: Shajan
authors.initials: S
authors.lastname: Peter
authors.forename: Luisa
authors.initials: L
authors.lastname: Baselgia
authors.forename: Finn
authors.initials: F
authors.lastname: Larsen
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Drewe
mesh_terms: 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
chemical_list: D054439:Ghrelin; D006728:Hormones; D007211:Indoles; D009842:Oligopeptides; D036361:Peptide Hormones; D019382:Human Growth Hormone; C582727:macimorelin; D014364:Tryptophan; D013007:Growth Hormone-Releasing Hormone