Naproxen-PC: a GI safe and highly effective anti-inflammatory.
We have been developing a family of phosphatidylcholine (PC)-associated NSAIDs, which appear to have improved GI safety and therapeutic efficacy in both rodent model systems and pilot clinical trials. As naproxen has been demonstrated to be associated with the lowest cardiovascular adverse events in comparison with both COX-2 selective inhibitors and conventional NSAIDs, we have been developing a Naproxen-PC formulation for evaluation in animal models and clinical trials. We have determined that an oil-based formulation of naproxen and triple strength soy lecithin provides excellent GI protection in both: 1) an acute NSAID-induced intestinal bleeding model in rats pretreated with L-NAME that are intragastrically administered a single dose of naproxen (at a dose of 50 mg/kg) vs the equivalent dose of Naproxen-PC; and 2) a more chronic model (at a naproxen dose of 25 mg/kg BID) in rats that have pre-existing hindpaw inflammation (induced with a intradermal injection of Complete Freund's Adjuvant/CFA). Both models demonstrate the superior GI safety of Naproxen-PC vs naproxen while this novel formulation had significant anti-inflammatory efficacy to reduce hindpaw edema and the generation of PGE(2) in the collected joint synovial fluid.


CONCLUSIONS
Naproxen-PC appears to induce significantly less GI injury and bleeding in two rodent model systems while maintaining anti-inflammatory and COX-inhibitory activity.
Lichtenberger
L M
LM
Department of Integrative Biology & Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, USA. Lenard.M.Lichtenberger@uth.tmc.edu
Romero
J J
JJ
Dial
E J
EJ
Moore
J E
JE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D054709:Lecithins / Q000737:chemistry*; D009288:Naproxen / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D013025:Glycine max / Q000737:chemistry; D013582:Synovial Fluid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D054709:Lecithins; D009288:Naproxen; D015232:Dinoprostone