Summary
In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng · kg−1 · min−1 was given for 6 h.
During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min.
During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased.
Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, β-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug-related alteration.
It is concluded that infusion of taprostene 25 ng · kg−1 · min−1 caused measurable inhibition of platelet function ex vivo.
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References
Barth H, Lintz W, Michel G, Osterloh G, Seipp U, Flohe L (1983) Inhibition of platelet aggregation by intravenous administration of the biochemically stable prostacyclin analogue CG 4203 in man. Naunyn-Schmiedeberg's Arch Pharmacol [Suppl] 324: R 60
Belch JJF, McKay A, McArdle B, Leiberman P, Pollock JG, Lowe GDO, Forbes CB, Prentice CRM (1983) Epoprostenol (prostacyclin) in severe arterial disease. A double blind trial. Lancet I: 315–317
Belch JJ, Greer I, McLaren L, Saniabadi AR, Miller S, Sturruck RD, Forbes CD (1984) The effects of intravenous ZK 36374, a stable prostacyclin analogue, on normal volunteers. Prostaglandins 28: 67–76
Cella G, Zahavi Z, DeHaas HA, Kakkar KA (1979) β-Tromboglobulin, platelet production time and platelet function in vascular disease. Br J Haematol 43: 127–136
Fitscha P, Kaliman J, Sinzinger H (1985) Platelet sensitivity and antiaggregatory prostaglandins (PGE1, D2, I2) in patients with peripheral vascular disease. Am J Hematol 19: 13–19
Fitscha P (1986) Prostaglandine in Pathogenese and Therapie der peripheren Verschlußkrankheit (PVK). In: Kraupp O, Sinzinger H, Widhalm K (eds), Atherogenesis 7. Maudrich, Vienna, Austria
Hladovec J, Rossmann P (1973) Circulating endothelial cells isolated together with platelets and the experimental modifications of of their counts in rats. Thromb Res 3: 665–671
Jouve R, Rolland PH, Delboy C, Mercier C (1984) Thromboxane B2, 6-keto-PGF1α, PGE2, PGF2α, and PGA1 plasma levels in arteriosclerosis obliterans: Relationship to clinical manifestations, risk factors and arterial pathoanatomy. Am Heart J 107: 45–52
Kaliman J, Fitscha P, Barth H, Sinzinger H (1987) Clinical benefit and prolongation of platelet half-life by CG 4203, a stable PGI2-analogue. In: Sinzinger H, Schrör K (eds) Prostaglandins in clinical research, Vol 242. Liss, NY, USA, pp 469–477
Longmore DB, Hoyle M, Gregory A, Bennett JG, Smith MA, Ossiand T, Jones WA (1981) Prostacyclin administration during cardiopulmonary bypass in man. Lancet I: 800–803
Maurin N (1985) Influence in platelet activity and red cell fluidity of prostacyclin (PGI2) and the stable prostacyclin analogues CG 4203 and CG 4205. Thromb Haemost 54: A 18
Maurin N (1987) Hemodialysis with the stable prostacyclin analogue CG 4203. In: Sinzinger H, Schrör K (eds) Prostaglandins in clinical research, Vol 242. Liss, NY, USA, pp 479–484
Michel G, Friderichs E, Müller B, Wilsmann K, Seipp U, Flohe L (1982) CG 4203 (new stable prostacyclin analogue): actions on platelets and blood pressure. 1st International Austrian Prostaglanding Meeting, Bad Ischl, Austria, A 26
Peskar BA, Anhut H, Kröner EE, Peskar BM (1979) Development, specifity and some applications of radioimmunoassays for prostaglandins and related compounds. In: Tillement IB (ed) Advances in pharmacology and therapeutics. Pergamon, Oxford, UK, pp 275–289
Placer ZA, Crusshman LL, Johnson CC (1966) Estimation of a product of lipid peroxidation (malondialdehyde) in biological systems. Anal Biochem 16: 359–365
Sinzinger H, Leithner C, Silberbauer K (1984) Rebound platelet activation during continuous epoprostenol infusion. Lancet II: 759–760
Sinzinger H, Fitscha P, Kaliman J, O'Grady J (1986) Search of the optimal PGI2-infusion protocol-advantages of a 6 hours intermittent infusion. Thromb Haemost 54: 85–126
Steinhauer HB, Barth H, Hörl HW, Schollmeyer P (1985) The stable prostacycin analogue CG 4203 as sole antithrombotic drug in hemodialysis (HD). Thromb Haemost 54: A 81
Strobel-Jäger E, Fitscha P, Kaliman J, Widhalm K, Sinzinger H (1986) Platelet half-life in comparison to other in-vivo platelet function parameters such as thromboxane B2, β-thromboglobulin and platelet factor 4 in patients with atherosclerotic lesions with and without hyperlipoproteinemia. VASA 15: 373–378
Szczeklik A, Nizankowski R, Skawinski S, Szeceklik J, Gluszko P, Gryglewski RJ (1979) Successful therapy of advanced arteriosclerosis obliterans with prostacyclin. Lancet I: 1111–1114
Wu KK, Hoak JC (1976) Spontaneous platelet aggregation in arterial insufficiency: mechanism and implications. Thromb Haemost 35: 702–703
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Virgolini, I., Fitscha, P., Sinzinger, H. et al. Effects of taprostene, a stable prostacyclin analogue, on haemodynamics, platelet function and arachidonate metabolism in healthy volunteers. Eur J Clin Pharmacol 38, 347–350 (1990). https://doi.org/10.1007/BF00315573
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DOI: https://doi.org/10.1007/BF00315573