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Pharmacokinetics and Pharmacodynamic Effects of an Oral Ghrelin Agonist in Healthy Subjects

Clinical Research Center, Department of Research (F.P., L.D., L.B., C.B., J.D.), Division of Gastroenterology (F.P., L.D., S.P., C.B.), and Department of Clinical Pharmacology and Toxicology (J.D.), University Hospital, 4031 Basel, Switzerland; and Ardana Bioscience Ltd. (C.M., F.L.), Edinburgh EH3 7HA, United Kingdom

Address all correspondence and requests for reprints to: Christoph Beglinger, M.D., Department of Gastroenterology, University Hospital, CH-4031 Basel, Switzerland. E-mail: beglinger{at}tmr.ch.

Context: 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.

Objectives: 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.

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

Subjects and 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.