Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers.
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.
Clinical Pharmacology, Bayer HealthCare AG, Pharma Research Centre, Aprather Weg 18a, 42096 Wuppertal, Germany. reiner.frey@bayerhealthcare.com
Reiner
R
Frey
Wolfgang
W
Mück
Sigrun
S
Unger
Ulrike
U
Artmeier-Brandt
Gerrit
G
Weimann
Georg
G
Wensing
D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004311:Double-Blind Method; D006162:Guanylate Cyclase / Q000378:metabolism*; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D006728:Hormones; D012083:Renin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D009638:Norepinephrine