Nitroflurbiprofen NicOx SA

Abstract

NicOx is developing nitroflurbiprofen (HCT-1026) as a non-steroidal anti-inflammatory drug (NSAID) which has the ability to release nitric oxide. It has completed phase I clinical trials as a potential treatment for inflammation and rheumatoid arthritis [198694]. In the trial, which took place at Queens Medical Center, Nottingham, UK, the drug showed excellent tolerability, as well as potent and long lasting serum thromboxane inhibition in healthy volunteers after single oral doses of 50 and 100 mg [243679]. A repeated dose endoscopic study showed that nitroflurbiprofen causes less gastrointestinal damage in healthy volunteers than flurbiprofen [265025,295029]. Although phase II studies in patients with musculoskeletal disorders were scheduled for 1997 [243679], it seems they have not yet commenced. The compound is as potent as conventional flurbiprofen, but is better tolerated in rats, dogs and rabbits when given orally or parenterally following either single or repeated doses [198694]. Unlike conventional NSAIDs, nitro-flurbiprofen is able to release NO and increase cGMP in endothelial cells, and to inhibit the expression of inducible nitric oxide synthase and endotoxin in the gastrointestinal tract [190759].