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 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 > or = 1 mg/kg i.v.. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1 mg/kg i.v., but the maximum lipase releasing effect at 3 mg/kg i.v. was identical for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at single i.v. doses up to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org 31540 (1 mg/kg s.c. for 9 days) revealed no influence on the lipase releasing effect of UFH (1 mg/kg i.v. 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.
Hoffmann
P
P
Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
Bernat
A
A
Dumas
A
A
Petitou
M
M
Hérault
J P
JP
Herbert
J M
JM
D000818:Animals; D004334:Drug Administration Schedule; D005227:Fatty Acids / Q000097:blood; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008049:Lipase / Q000097:blood / Q000187:drug effects*; D008297:Male; D009844:Oligosaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA; D008049:Lipase