Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis

Six patients, not previously treated, with classical seropositive rheumatoid arthritis and highly active synovitis of one or both knee joints were treated with 4 g of 40% benorylate suspension twice daily for a period of 9--14 days prior to synovectomy. Blood samples were taken at scheduled times during administration of the drug. At operation, synovial fluid and tissue samples were taken and their salicylate, paracetamol and benorylate content measured. Plasma levels of salicylate and paracetamol were, in general, significantly higher than the concentration of these metabolites in the synovial fluid. Benorylate was found in the synovial tissues concentrated especially in the highly inflamed synovial villi. It is probable that benorylate and its metabolites penetrate the synovia but further studies are needed to determine if the metabolites are concentrated in the different synovial cell layers in the same way as benorylate itself. It is possible that part of the clinical effect of benorylate is due to its presence in the synovial tissue and that it has a direct effect in vivo on the synovial membrane. It is also possible that the pharmacokinetic properties of benorylate permit it to enter cell layers inaccessible to its metabolites.