Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects

Can J Physiol Pharmacol. 1996 Aug;74(8):887-93. doi: 10.1139/cjpp-74-8-887.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Blood Pressure / drug effects
  • Double-Blind Method
  • Epoprostenol / adverse effects
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / pharmacokinetics
  • Epoprostenol / pharmacology
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Male
  • Placebos
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / pharmacology*

Substances

  • Placebos
  • Platelet Aggregation Inhibitors
  • beraprost
  • Epoprostenol