In vitro distribution of ketoprofen enantiomers in articular tissues of osteoarthritic patients

The distribution of ketoprofen enantiomers in joint tissues was studied as a function of their relative tissular affinities using the multi-chamber di stribution dialysis system described by Bickel et at. Selected off-cuts of synovial membrane. joint capsule, cartilage and ligament were obtained from ten patients suffering from osteoarthritis of the knee (n = 3) or hip (n = 7). Sorensen solution (4 ml) spiked with racemic ketoprofen (2 mug ml(-1)) was dialysed against I ml of the four solutions of tissue homogenates (0.4 g ml(-1)). Ketoprofen enantiomers were quantified in buffer and tissue sol utions by high-performance liquid chromatography. The distribution of ketop rofen enantiomers in the Bickel's multi-compartment model indicated that th ere was a non-stereoselective affinity of ketoprofen enantiomers for their potential target tissues. Despite the interindividual variability in articu lar tissues, the concentrations (+/-S.D.) of R- and S-ketoprofen were signi ficantly higher in synovial membrane (8.69 (4.76) mug g(-1) for S, 9.14 (5. 57) mug g(-1) for R), joint capsule (5.71 (2.49) mug g(-1) for S, 5.49 (2.6 2) mug g(-1) for R) and ligament (6.28 (3.61) mug g(-1) for S. 6.40 (3.64) mug g(-1) for R) than in articular cartilage (3.67 (1.75) mug g(-1) for S, 3.70 (1.67) mug g(-1) for R). There were no significant differences in the distribution of R- and S-ketoprofen between the solutions of joint capsule, synovium and ligament tissues. These data may be related to differences in ketoprofen affinity for the different constituents of joints. This in vitr o distribution profile is similar to that reported in vivo for other non-st eroidal anti-inflammatory drugs. (C) 2001 Elsevier Science B.V. All rights reserved.