THE SYNTHETIC PENTASACCHARIDE SR-90107A ORG-31540 DOES NOT RELEASE LIPASE ACTIVITY INTO THE PLASMA

The present study was designed to find out whether the synthetic penta saccharide SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an antithrombotic agent, influences lipoprotein met abolism in rats as determined by plasma triglyceride (TG) lipase activ ity. A comparison with three clinically used sulphated polysaccharides - unfractionated heparin (UFH), low molecular weight heparin (LMWH) a nd pentosan polysulphate (PPS)- was performed. UFH evoked a dose-depen dent increase in plasma TG lipase activity which plateaued at doses gr eater than or equal to 1 mg/kg iv. PPS and LMWH demonstrated a lower e fficacy than heparin at 0.3 and 1 mg/kg iv, but the maximum lipase rel easing effect at 3 mg/kg iv was identical for UFH, PPS and LMWH. SR 90 107A/Org 31540 did not release TG lipase activity at single iv doses u p to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org 31540 (1 mg /kg sc for 9 days) revealed no influence on the lipase releasing effec t of UFH(1 mg/kg iv on day 10). These results demonstrate that SR 9010 7A/Org 31540 does not influence lipid metabolism in rats through lipas e release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and LMWH in clinical situations where an anticoagulant/antith rombotic effect is desired, but both an increase in plasma free fatty acids and atherogenic alterations of lipoprotein metabolism are consid ered harmful. (C) 1997 Elsevier Science Ltd.