Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers

J Clin Pharmacol. 2008 Aug;48(8):926-34. doi: 10.1177/0091270008319793. Epub 2008 Jun 2.

Abstract

The aim of the study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of BAY 63-2521, a new drug in development for pulmonary hypertension. Fifty-eight healthy male volunteers received a single oral dose of BAY 63-2521 (0.25-5 mg) or placebo. No serious adverse events were reported; there were no life-threatening events. Heart rate over 1 minute, an indicator of the effect of a vasodilating agent on the cardiovascular system in healthy subjects, was increased dose dependently versus placebo at BAY 63-2521 doses of 1 to 5 mg (P < .01). Mean arterial and diastolic pressures were decreased versus placebo at doses of 1 mg (P < .05) and 5 mg (P < .01). Systolic pressure was not significantly affected. BAY 63-2521 was readily absorbed and exhibited dose-proportional pharmacokinetics. The pharmacodynamic and pharmacokinetic properties of BAY 63-2521 suggest that it can offer a unique mode of action in the treatment of pulmonary hypertension.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacokinetics*
  • Antihypertensive Agents / pharmacology*
  • Area Under Curve
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Cyclic GMP / blood
  • Double-Blind Method
  • Guanylate Cyclase / metabolism*
  • Half-Life
  • Heart Rate / drug effects
  • Hormones / blood
  • Humans
  • Male
  • Norepinephrine / blood
  • Renin / blood

Substances

  • Antihypertensive Agents
  • Hormones
  • Renin
  • Guanylate Cyclase
  • Cyclic GMP
  • Norepinephrine