CICAPROST, AN ORALLY-ACTIVE PROSTACYCLIN ANALOG - ITS EFFECTS ON PLATELET-AGGREGATION AND SKIN BLOOD-FLOW IN NORMAL VOLUNTEERS

1 Prostacyclin (PGI2) and its analogues may be useful in peripheral vascular disease. However, most have to be given intravenously due to their metabolic instability. 2 We have investigated the pharmacological effects of cicaprost, a synthetic PGI2 analogue which is metabolically stable and bioavailable after oral administration, in eight healthy male volunteers. 3 This was a double-blind, placebo-controlled, cross-over study. The volunteers were given either placebo, 5 mug, 7.5 mug or 10 mug cicaprost (at 09.00 h, 14.00 h, 19.00 h and again at 09.00 h the following day) on four separate occasions each 14 days apart. 4 Platelet aggregation induced by collagen and ADP in platelet rich plasma (PRP) and whole blood were measured prior to and 1 h after the trial medication. Laser Doppler flowmetry measured skin blood flow on the face before and after medication. 5 There was a statistically significant dose relationship in the inhibition of platelet aggregation induced by 2 mum ADP and 0.4 mug ml-1 collagen in PRP and 2 mum ADP and 0.6 mug ml-1 collagen in whole blood by cicaprost (P = 0.008, P = 0.34, P = 0.011 and P = 0.036, respectively). The threshold dose was 7.5 mug. Attenuation of anti-platelet effects was seen with the 14.00 h and 19.00 h doses. This may be due to a decrease in absorption after meals or to the development of tachyphylaxis. 6 Similar dose dependent effects of cicaprost on skin blood flow were also found (P = 0.01 and P = 0.006 for maximum output signal and red blood cell flux, respectively). The threshold dose was 7.5 mug. 7 In conclusion, cicaprost has significant anti-platelet and vasodilatory effects when given in doses of 7.5 mug and 10 mug three times a day in healthy male volunteers.