Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis

Abstract

Twenty patients with definite or classical rheumatoid arthritis and chronic knee effusions were each given an oral dose of 4 g benorylate as the 40% suspension. Synovial fluid and plasma samples were obtained up to 9 hours after drug administration and assayed for their salicylate and benorylate content. A mean peak benorylate plasma level of 2.18 +/- 0.19 mug/ml occurred 30 min after drug administration but declined rapidly and benorylate was virtually undetectable in the plasma 90 min later. The mean peak benorylate synovial fluid level of 0.74 +/- 0.21 mug/ml occurred 3 hours after drug administration but the concentration remained steady for at least a further 9 hours. A mean peak plasma salicylate level of 119 +/- 14.2 mug/ml and mean peak synovial fluid salicylate level of 78 +/- 13.6 mug/ml occurred 3 hours after benorylate administration. Both levels declined slowly over some hours. This study shows that benorylate per se readily enters the synovial fluid in patients with rheumatoid arthritis and continues to accumulate there even when undetectable in the plasma. It is possible that the lipophilic nature of the benorylate molecule facilitates its uptake by the inflamed synovial tissue.