Effect of food on the pharmacokinetics and pharmacodynamics of an oral ghrelin agonist (ARD-07) in healthy subjects.
ARD-07 (also known as EP01572) is a peptidomimetic growth hormone secretagogue that can be administered orally. The primary objective of this study is to determine the effects of a meal on the oral bioavailability of ARD-07 after a single oral dose (0.5 mg/kg). In addition, the pharmacodynamic effects (growth hormone release, insulin-like growth factor-1 concentrations) and the tolerability of ARD-07 are investigated in this open-label, randomized, crossover study. Sixteen healthy subjects (8 males, 8 females) receive ARD-07 on 2 different days; the treatment consists of a single oral dose of ARD-07 (0.5 mg/kg body weight), once with and the second day without a test meal. Plasma kinetics of ARD-07 and pharmacodynamic effects are quantified by specific assays. Results are given as mean +/- SEM: The area under the curve for 0 to 24 hours is approximately twice as high without food (27.8 +/- 4.1) than with food (13.7 +/- 1.2; P = .002). The maximum observed ARD-07 concentration relative to dose administration (C(max)) is more than twice as high without food (10.6 +/- 1.6 ng/mL) than with food (4.4 +/- 0.5 ng/mL; P = .001). C(max) of growth hormone occurs at a significantly (P = .001) later stage with food (C(max) = 13.0 +/- 3.5 ng/mL) than without food (37.1 +/- 5.3 ng/mL). Food has a marked effect on the absorption of ARD-07: there is a significant difference in bioavailability between administration of oral ARD-07 with and without food.
MacLean
Carol M
CM
Department of Gastroenterology, University Hospital, Basel, Switzerland.
Casanova
Anna-Tina
AT
Baselgia-Jeker
Luisa
L
Neave
Nicola
N
Larsen
Finn
F
Skillern
Laurence
L
Drewe
Juergen
J
Beglinger
Christoph
C
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions; D054439:Ghrelin / Q000819:agonists*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007211:Indoles; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives
D054439:Ghrelin; D007211:Indoles; D009842:Oligopeptides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C582727:macimorelin; D014364:Tryptophan