Inhibition of platelet aggregation with intravenous and oral administration of a carboprostacyclin analogue, 15-cyclopentyl-ω-pentanor-5(E)-carbacyclin (ONO 41483) in man

Abstract

Intravenous and oral administration of a chemically stable carboprostacyclin analogue, 15-cyclopentyl-ω-pentanor-5(E)-carbacyclin (ONO 41483), resulted in ex-vivo inhibition of ADP-induced platelet aggregation in man. The maximum tolerated intravenous dose was 2.5 ng/kg/min for 1 hour and this produced a mean of 27.1% inhibition in 3 volunteers. For oral administration the tolerated single dose was 200 μg. At this dose, there was 56.3% inhibition of aggregation (mean of 3 results). High oral (400 μg) and intravenous doses (5 and 10 ng/kg/min for 1 hour) of ONO 41483, which caused marked inhibition of aggregation (ranging 39-100%), was accompanied by flushing of face and extremities, headache and phlebitis. However, none of the doses tested produced significant changes in arterial blood pressure or heart rate.