Inhibition of platelet aggregation with oral administration of a stable prostacyclin analogue (carboprostacyclin) in baboons

Abstract

A prostacyclin (PGI 2) analog, carboprostacyclin, was recently shown to be a stable compound with pharmacological activity in the baboon when given by mouth. The present study tested its inhibitory activity on platelet aggregation in six baboons, in doses of 0.25 to 2.0 mg./kg. administered through stomach tube. The degree to which a pretested submaximal concentration of ADP-induced platelet aggregation was inhibited at various time intervals ( 1/2 - 4 hr) after giving carboprostacyclin was expressed as a percentage of this control. A dose dependent inhibition of platelet aggregation was demonstrated. In four baboons receiving maximal doses (2 mg./kg.) inhibition was 35%, 57.7%, 91.5%, and 95.4% respectively. The effects lasted from 1.5 hours to 4 hours. There was no alteration of arterial blood pressure but an increase in heart rate in 3 out of 4 animals receiving the maximal dose. Prostacyclin itself exerts similaar effects on the platelets of man and baboons. Thus, this study suggests that carboprostacyclin given orally is likely to be active in man. Ellis J. van Slyck, M.D. Detroit, Mich.