Different in vitro activity of flurbiprofen and its enantiomers on human articular cartilage

• Published in: Farmaco (Società chimica italiana : 1989) 2003-12, Vol.58 (12), p.1339-1344
• Main Authors: Panico, A.M., Cardile, V., Vittorio, F., Ronsisvalle, G., Scoto, G.M., Parenti, C., Gentile, B., Morrone, R., Nicolosi, G.
• Format: Article
• Language: English
• Subjects: ( S)-(+)-Flurbiprofen; Arthritis; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cartilage; Cartilage, Articular - cytology; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - secretion; Cells, Cultured; Flurbiprofen - analogs & derivatives; Flurbiprofen - chemistry; Flurbiprofen - pharmacology; GAGs; Glycosaminoglycans - antagonists & inhibitors; Glycosaminoglycans - secretion; Humans; Interleukin-1 - pharmacology; Medical sciences; Pharmacology. Drug treatments; Stereoisomerism
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(03)00196-4

The 2-arylpropionic acid derivatives or ‘profens’ are an important group of non-steroidal anti-inflammatory drugs that have been used for the symptomatic treatment of various forms of arthritis. These compounds are chiral and the majority of them are still marketed as racemate although it is known that the ( S)- form is the principal effective in the cyclooxygenase inhibition. However, recent findings suggest that certain pharmacological effect of 2-arylpropionic acids cannot be attributed exclusively to the ( S)-(+) enantiomer. To obtain further insights into the pharmacological effect of profens, the present study investigated the influence of racemic and pure enantiomers of flurbiprofen on the production of nitric oxide and glycosaminoglycans, key molecules involved in cartilage destruction. The culture of human articular cartilage stimulated by interleukin-1β (IL-1β), which plays an important role in the degradation of cartilage, has been established, as a profit experimental model, for reproducing the mechanisms involved in the pathophysiology of arthritic diseases. Our results show that mainly ( S)-(+)-flurbiprofen decreases, at therapeutically concentrations, the IL-1β induced cartilage destruction.