Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects.
The antiaggregation and hemodynamic effects of the new prostacyclin analogue beraprost sodium were investigated in a randomized, placebo-controlled, double-blind clinical trial of Latin-square design. Twelve healthy Caucasian males randomly received 8-day oral treatments of 20, 40, and 60 micrograms of beraprost sodium and a placebo. One-week washout periods followed each treatment. Pharmacokinetic and pharmacodynamic measurements were performed on days 1 and 8 for each period of treatment. All three doses of beraprost sodium significantly inhibited platelet aggregation on day 8 (compared with placebo) during the 1st h after drug intake. Incubation of the 60-micrograms beraprost sodium samples with ADP (2, 5, and 10 microM) and collagen (1.25 micrograms/mL) decreased platelet aggregation by 10, 19, 16, and 6 +/- 4% (mean +/- SE), respectively, compared with placebo. No significant hemodynamic effects on blood pressure, heart rate, and digital pulse were observed. The 60-micrograms dose of beraprost sodium did significantly decrease the IRZ index (which may reflect the left ventricular pre-ejection period) on days 1 and 8. Some subjects experienced headache and facial flushing, effects that were dose dependent and reversible. Beraprost sodium at 20- to 60-micrograms doses exerts platelet antiaggregation (day 8 of therapy) and slight hemodynamic (days 1 and 8 of treatment) effects in Caucasian males. Beraprost sodium hemodynamic effects and potential benefits in patients with cardiovascular disease should be explored further.
Nony
P
P
Clinical Pharmacology Unit, Cardiovascular Hospital, Lyon, France.
Ffrench
P
P
Girard
P
P
Delair
S
S
Azoulay
S
S
Girre
J P
JP
Dechavanne
M
M
Boissel
J P
JP
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D010919:Placebos; D010975:Platelet Aggregation Inhibitors; C048081:beraprost; D011464:Epoprostenol