title: In vitro distribution of ketoprofen enantiomers in articular tissues of osteoarthritic patients.
abstract: The distribution of ketoprofen enantiomers in joint tissues was studied as a function of their relative tissular affinities using the multi-chamber distribution dialysis system described by Bickel et al. 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). Sörensen solution (4 ml) spiked with racemic ketoprofen (2 microg ml(-1)) was dialysed against 1 ml of the four solutions of tissue homogenates (0.4 g ml(-1)). Ketoprofen enantiomers were quantified in buffer and tissue solutions by high-performance liquid chromatography. The distribution of ketoprofen enantiomers in the Bickel's multi-compartment model indicated that there was a non-stereoselective affinity of ketoprofen enantiomers for their potential target tissues. Despite the interindividual variability in articular tissues, the concentrations (+/-S.D.) of R- and S-ketoprofen were significantly higher in synovial membrane (8.69 (4.76) microg g(-1) for S, 9.14 (5.57) microg g(-1) for R), joint capsule (5.71 (2.49) microg g(-1) for S, 5.49 (2.62) microg g(-1) for R) and ligament (6.28 (3.61) microg g(-1) for S, 6.40 (3.64) microg g(-1) for R) than in articular cartilage (3.67 (1.75) microg g(-1) for S, 3.70 (1.67) microg 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 vitro distribution profile is similar to that reported in vivo for other non-steroidal anti-inflammatory drugs.
authors.affiliation: Laboratoire de Therapeutique, Department of Clinical Pharmacology and Therapeutics EA525, Université Victor Segalen & Groupe Hospitalier Pellegrin, BP 38, 146 rue Leo Saignat, 33076 Cedex, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Lagrange
authors.forename: T
authors.initials: T
authors.lastname: Fabre
authors.forename: F
authors.initials: F
authors.lastname: Péhourcq
authors.forename: A
authors.initials: A
authors.lastname: Durandeau
authors.forename: B
authors.initials: B
authors.lastname: Bannwarth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002358:Cartilage, Articular / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007660:Ketoprofen / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D007660:Ketoprofen