Pharmacokinetics and pharmacodynamic effects of ABT‐627, an oral ETA selective endothelin antagonist, in humans

• Published in: British journal of clinical pharmacology 2000-06, Vol.49 (6), p.562-573
• Main Authors: Verhaar, Marianne C., Grahn, Amy Y., Van Weerdt, Anton W. M., Honing, Marina L. H., Morrison, Paul J., Yang, Yonghong P., Padley, Robert J., Rabelink, Ton J.
• Format: Article
• Language: English
• Subjects: ABT‐627; Adult; Aged; Area Under Curve; Atrasentan; Biological Availability; endothelin antagonist; Endothelin Receptor Antagonists; endothelins; Endothelins - antagonists & inhibitors; Endothelins - metabolism; Forearm - blood supply; Half-Life; Hemodynamics - drug effects; Hemodynamics - physiology; Humans; Male; Middle Aged; Pharmacokinetics/Pharmacodynamics; Pyrrolidines - pharmacokinetics; Pyrrolidines - pharmacology; Receptor, Endothelin A; Regional Blood Flow - physiology; Vasoconstriction - drug effects
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2000.00171.x

Aims  Endothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT‐627 in healthy humans. Methods  Healthy volunteers were included in two studies with cross‐over design. Subjects received single or multiple dose (an 8 day period) administration of oralABT‐627 or matched placebo, in a dose range of 0.2–40 mg. The pharmacokinetics of ABT‐627 were described and its effects on systemic haemodynamics under resting conditions and on forearm vasoconstriction in response to ET‐1 were assessed. Results  ABT‐627 was generally well tolerated in both studies, with transient headache being the most reported adverse event (in 62%vs 4% during placebo, P