Pharmacokinetics of the R(-) and S(+) enantiomers of ibuprofen in the serum and synovial fluid of arthritis patients.

Eight patients with arthritis and knee effusions received 13 doses of a single 800-mg ibuprofen tablet every 8 hours. Serum and synovial fluid samples were obtained after the first and last doses and assayed for the R(-) and S(+) enantiomers of ibuprofen by a stereospecific assay. Since only S(+)-ibuprofen inhibits cyclo-oxygenase, a description of the time course of this isomer in synovial fluid is needed for the development of suitable pharmacodynamic models. The isomers were significantly different with respect to peak concentrations and areas under the concentration-time curves (AUC) in synovial fluid levels. No significant accumulation of either isomer was observed in serum or synovial fluid levels between the first and the last doses. The steady-state concentration of both isomers fluctuated less in synovial fluid than in plasma, and the synovial fluid concentrations of the S(+) isomer were about twice that of the R(-) isomer. The mean synovial albumin concentration was about 60% of the serum albumin concentration, and the steady-state isomer AUC values in synovial fluid were significantly correlated with the corresponding serum values after the differences between the two fluids with respect to albumin concentration were corrected. The authors conclude that binding of the isomers to albumin and the serum-synovial fluid albumin ratio controls the steady-state distribution of the ibuprofen isomers into synovial fluid. The ramifications of these findings in the development of satisfactory concentration-response relationships are discussed.