Effect of Food on the Pharmacokinetics and Pharmacodynamics of an Oral Ghrelin Agonist (ARD-07) in Healthy Subjects

被引:9
作者
MacLean, Carol M. [3 ]
Casanova, Anna-Tina [2 ]
Baselgia-Jeker, Luisa [2 ]
Neave, Nicola [3 ]
Larsen, Finn [3 ]
Skillern, Laurence [3 ]
Drewe, Juergen [4 ]
Beglinger, Christoph [1 ,2 ]
机构
[1] Univ Hosp, Dept Gastroenterol, CH-4031 Basel, Switzerland
[2] Univ Hosp, Dept Biomed, Clin Res Ctr, CH-4031 Basel, Switzerland
[3] Ardana Biosci Ltd, Edinburgh, Midlothian, Scotland
[4] Univ Hosp, Dept Clin Pharmacol, CH-4031 Basel, Switzerland
基金
瑞士国家科学基金会;
关键词
Ghrelin; growth hormone; humans; pharmacokinetics; pharmacodynamics; MOLECULAR-WEIGHT DEPENDENCE; ABSORPTION; DELIVERY; PEPTIDE; INSULIN; CALCITONIN; APPETITE;
D O I
10.1177/0091270008330160
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 with-out 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.
引用
收藏
页码:553 / 559
页数:7
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