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.
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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)
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Chemical References |
- Fibrinolytic Agents
- SC 39902
- Epoprostenol
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Topics |
- Animals
- Blood Platelets
(drug effects)
- Blood Pressure
(drug effects)
- Dogs
- Drug Evaluation, Preclinical
- Epoprostenol
(administration & dosage, pharmacology)
- Fibrinolytic Agents
- Male
- Rats
- Renal Dialysis
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