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Effect of Food on the Pharmacokinetics and Pharmacodynamics of an Oral Ghrelin Agonist (ARD‐07) in Healthy Subjects
Author(s) -
MacLean Carol M.,
Casanova AnnaTina,
BaselgiaJeker Luisa,
Neave Nicola,
Larsen Finn,
Skillern Laurence,
Drewe Juergen,
Beglinger Christoph
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008330160
Subject(s) - bioavailability , crossover study , pharmacokinetics , pharmacodynamics , meal , oral administration , ghrelin , medicine , tolerability , secretagogue , endocrinology , pharmacology , hormone , insulin , placebo , adverse effect , alternative medicine , pathology
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.