Evaluation of a stable 5-F prostacyclin analogue as an antithrombotic agent in haemodialysis.

Abstract

Prostacyclin has been used as a substitute for heparin in renal dialysis because of its potent antiplatelet activity and its short half-life. However, it is difficult to use because of its instability in neutral buffer and its hypotensive activity at antithrombotic doses. SC-39902, a 5-F prostacyclin analogue, has an ED50 of 17.7 micrograms/kg i.v. against ADP-induced thrombocytopenia in rats. The ED25 for hypotensive activity is 7.0 micrograms/kg i.v. The therapeutic index (blood pressure ED25/antiplatelet ED50) of 0.40 is 3.6 times better than that of PGI2 (0.11). SC-39902 supports clot-free dialysis in dogs at 4.0 micrograms/kg/min (ED100 for dialysis) with a 26% change in blood pressure at the 100% effective dose as compared with 0.052 microgram/kg/min required for PGI2 with a 32% change in blood pressure. The authors conclude that SC-39902 will provide the desirable antiplatelet/antithrombotic activities of PGI2 without instability and buffer incompatability problems. However, at the ED100 for dialysis, SC-39902 does have haemodynamic activity and, thus, a therapeutic index which is greater than four times that of PGI2 in rats is required for a PGI2 analogue to have less hypotensive activity during dialysis.

• Authors: N S Nicholson, S L Smith, B B Taite, A Krueger, G C Fuller
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 12 Issue 5 Pg. 371-5 ( 1986) ISSN: 0378-6501 [Print] Switzerland
• PMID: 3522158 (Publication Type: Journal Article)

Chemical References

• Fibrinolytic Agents
• SC 39902
• Epoprostenol

Topics

• Animals
• Blood Platelets (drug effects)
• Blood Pressure (drug effects)
• Dogs
• Drug Evaluation, Preclinical
• Epoprostenol (administration & dosage, pharmacology)
• Fibrinolytic Agents
• Male
• Rats
• Renal Dialysis