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. 1993 Jun;35(6):643–647. doi: 10.1111/j.1365-2125.1993.tb04195.x

Cicaprost, an orally active prostacyclin analogue: its effects on platelet aggregation and skin blood flow in normal volunteers.

J J Belch 1, M McLaren 1, C S Lau 1, I R Mackay 1, A Bancroft 1, J McEwen 1, J M Thompson 1
PMCID: PMC1381609  PMID: 8329292

Abstract

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 micrograms, 7.5 micrograms or 10 micrograms 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 microM ADP and 0.4 microgram ml-1 collagen in PRP and 2 microM ADP and 0.6 microgram 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 micrograms. 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 micrograms. 7. In conclusion, cicaprost has significant anti-platelet and vasodilatory effects when given in doses of 7.5 micrograms and 10 micrograms three times a day in healthy male volunteers.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  2. Belch J. J., Greer I., McLaren M., Saniabadi A. R., Miller S., Sturrock R. D., Forbes C. D. The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers. Prostaglandins. 1984 Jul;28(1):67–77. doi: 10.1016/0090-6980(84)90114-x. [DOI] [PubMed] [Google Scholar]
  3. Belch J. J., Newman P., Drury J. K., McKenzie F., Capell H., Leiberman P., Forbes C. D., Prentice C. R. Intermittent epoprostenol (prostacyclin) infusion in patients with Raynaud's syndrome. A double-blind controlled trial. Lancet. 1983 Feb 12;1(8320):313–315. doi: 10.1016/s0140-6736(83)91624-0. [DOI] [PubMed] [Google Scholar]
  4. Fiessinger J. N., Schäfer M. Trial of iloprost versus aspirin treatment for critical limb ischaemia of thromboangiitis obliterans. The TAO Study. Lancet. 1990 Mar 10;335(8689):555–557. doi: 10.1016/0140-6736(90)90346-7. [DOI] [PubMed] [Google Scholar]
  5. Hildebrand M., Staks T., Schütt A., Matthes H. Pharmacokinetics of 3H-cicaprost in healthy volunteers. Prostaglandins. 1989 Feb;37(2):259–273. doi: 10.1016/0090-6980(89)90062-2. [DOI] [PubMed] [Google Scholar]
  6. Saniabadi A. R., Fisher T. C., McLaren M., Belch J. F., Forbes C. D. Effect of dipyridamole alone and in combination with aspirin on whole blood platelet aggregation, PGI2 generation, and red cell deformability ex vivo in man. Cardiovasc Res. 1991 Mar;25(3):177–183. doi: 10.1093/cvr/25.3.177. [DOI] [PubMed] [Google Scholar]
  7. Saniabadi A. R., Lowe G. D., Forbes C. D., Prentice C. R., Barbenel J. C. Platelet aggregation studies in whole human blood. Thromb Res. 1983 Jun 15;30(6):625–632. doi: 10.1016/0049-3848(83)90271-2. [DOI] [PubMed] [Google Scholar]
  8. Sinzinger H., Silberbauer K., Horsch A. K., Gall A. Decreased sensitivity of human platelets to PGI2 during long-term intraarterial prostacyclin infusion in patients with peripheral vascular disease--a rebound phenomenon? Prostaglandins. 1981 Jan;21(1):49–51. doi: 10.1016/0090-6980(81)90195-7. [DOI] [PubMed] [Google Scholar]
  9. Skuballa W., Schillinger E., Stürzebecher C. S., Vorbrüggen H. Synthesis of a new chemically and metabolically stable prostacyclin analogue with high and long-lasting oral activity. J Med Chem. 1986 Mar;29(3):313–315. doi: 10.1021/jm00153a001. [DOI] [PubMed] [Google Scholar]
  10. Yardumian D. A., Isenberg D. A., Rustin M., Belcher G., Snaith M. L., Dowd P. M., Machin S. J. Successful treatment of Raynaud's syndrome with Iloprost, a chemically stable prostacyclin analogue. Br J Rheumatol. 1988 Jun;27(3):220–226. doi: 10.1093/rheumatology/27.3.220. [DOI] [PubMed] [Google Scholar]

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