Plasma and synovial fluid concentrations of diclofenac sodium and its hydroxylated metabolites during once-daily administration of a 100 mg slow-release formulation.

Plasma and knee joint synovial fluid (SF) concentration of diclofenac sodium and its hydroxylated metabolites were measured after chronic dosing with the 100 mg polymer matrix formulation. Peak concentrations were reached in plasma and SF roughly after administration. Plasma concentrations then fell rapidly, but concentrations in SF were maintained for up to 25 h. The active metabolite was present in both fluids throughout the study period. The slow-release form showed a longer plasma/SF equilibration time than the conventional tablet had in a previous study. Prostaglandin E1 and F2 alpha concentrations were lower in the early post-dose period but did not correlate with drug concentrations.