Stereoselective distribution of tiaprofenic acid in synovium and cartilage in osteoarthritic patients.
OBJECTIVE
In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared.


METHODS
The distribution of tiaprofenic acid in synovium and in cartilage was studied 25 h after administering the racemic drug for 2 days (600 mg of a sustained-release preparation, once daily), in 12 inpatients with osteoarthritis of the hip requiring arthroplasty. Enantiomers were quantified in plasma and freeze-ground tissues by a chiral HPLC assay.


RESULTS
Plasma concentrations of the dextrorotatory (R) enantiomer (0.40 microgram/ml) were higher than those of its antipode. The concentration of racemate in synovium (in dried and fresh tissues, 150% and 40%, respectively, of the concentration in plasma) was much higher than that in cartilage (in dried tissues 32% of the plasma concentration). The ratio of the active, dextrorotatory (R) enantiomer to its antipode was higher in synovial tissue than in plasma.


CONCLUSIONS
Tiaprofenic acid is distributed stereoselectively in plasma and synovium, which contain a higher concentration of the active, dextrorotatory (R) enantiomer. In cartilage, it reaches only a very low concentration.
Lapicque
F
F
Laboratoire de Pharmacologie, Vandoeuvre les Nancy, France.
Mainard
D
D
Gillet
P
P
Payan
E
E
Bannwarth
B
B
Netter
P
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D002356:Cartilage / Q000378:metabolism*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008968:Molecular Conformation; D015207:Osteoarthritis, Hip / Q000188:drug therapy*; D011422:Propionates / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013583:Synovial Membrane / Q000378:metabolism*; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011422:Propionates; C021270:tiaprofenic acid