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

• Published in: Thrombosis research 1997-05, Vol.86 (4), p.325-332
• Main Authors: Hoffmann, P, Bernat, A, Dumas, A, Petitou, M, Hérault, J.P, Herbert, J.M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Drug Administration Schedule; Fatty Acids - blood; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - pharmacology; heparin; Injections, Intravenous; Lipase - blood; Lipase - drug effects; low molecular weight heparin; Male; Medical sciences; Oligosaccharides - administration & dosage; Oligosaccharides - pharmacology; pentosan polysulphate; Pharmacology. Drug treatments; plasma lipase activity; Rats; Rats, Sprague-Dawley; SR 90107A/Org 31540
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(97)00075-3

The present study was designed to find out whether the synthetic pentasaccharide SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an antithrombotic agent, influences lipoprotein metabolism in rats as determined by plasma triglyceride (TG) lipase activity. A comparison with three clinically used sulphated polysaccharides - unfractionated heparin (UFH), low molecular weight heparin (LMWH) and pentosan polysulphate (PPS) - was performed. UFH evoked a dose-dependent increase in plasma TG lipase activity which plateaued at doses ≥ 1 mg/kg iv. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1 mg/kg iv, but the maximum lipase releasing effect at 3 mg/kg iv was identical for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at single iv doses up 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 effect of UFH (1 mg/kg iv on day 10). These results demonstrate that SR 90107A/Org 31540 does not influence lipid metabolism in rats through lipase release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and LMWH in clinical situations where an anticoagulant/antithrombotic effect is desired, but both an increase in plasma free fatty acids and atherogenic alterations of lipoprotein metabolism are considered harmful. © 1997 Elsevier Science Ltd