The effects of itnravenous ZK36-374, a stsable prostacyclin analogue, on normal volunteers

Prostacyclin (PGI₂) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivatives with a similar action to PGI₂; however, it is chemically stable and has less of a hypotensive action.We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. β-thromboglobulin, 6-keto-PGF_1α and TXB₂ were measuerd by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2μm AdP and 2μg collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2μm ADP and 0.5 μg collagen. βTG also fell significantly, as did the levels of 6-keto-PGF_1α and TXB₂. Fibrinolysis, blood viscosity, and red cell deformability were unchanged.ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.