Critical evaluation of the in vivo selectivity between hypotensive and platelet antiaggregating actions of iloprost and prostacyclin in beagle dogs

Arch Int Pharmacodyn Ther. Jul-Aug 1989;300:281-91.

Abstract

We compared the hypotensive and antiaggregatory effects of PGI2 and iloprost using our computerized aggregometric system. The concentration producing 50% inhibition (IC50) of ADP-induced platelet aggregation in vitro was 0.35 +/- 0.15 nM for PGI2 and 0.56 +/- 0.2 nM for iloprost (n = 5). The in vivo antiaggregatory activity was measured with a modified filtration pressure technique in anaesthetized beagle dogs. PGI2 was equipotent with iloprost in inhibiting platelet aggregation in vivo (ED25 = 0.23 +/- 0.04 nmol/kg; 0.26 +/- 0.05 nmol/kg, respectively). At the same time, PGI2 was twice as potent as iloprost in decreasing the mean arterial blood pressure (ED25 = 0.41 +/- 0.12 nmol/kg; 0.82 +/- 0.17 nmol/kg, respectively). The antiaggregatory and hypotensive effects of iloprost lasted longer in each experiment than those of PGI2; this difference reached the level of significance in the highest bolus dose range. The in vivo selectivity ratios (hypotensive potency/antiaggregatory potency) of iloprost and PGI2 were 0.32 and 0.67, respectively. The results indicate that 1) in anaesthetized beagles iloprost is somewhat more selective than PGI2 in inhibiting platelet aggregation (p less than 0.05); 2) our aggregometric system might be useful for quantitative and rapid determination of the in vivo selectivity of the new PGI2 analogues in anaesthetized beagles.

MeSH terms

  • Anesthesia
  • Animals
  • Blood Pressure / drug effects*
  • Dogs
  • Dose-Response Relationship, Drug
  • Epoprostenol / pharmacology*
  • Female
  • Iloprost
  • In Vitro Techniques
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors*

Substances

  • Platelet Aggregation Inhibitors
  • Epoprostenol
  • Iloprost