Stereoselective disposition of ibuprofen enantiomers in synovial fluid.
The simultaneous disposition of the enantiomers of ibuprofen in synovial fluid and plasma was studied in eight patients with arthritis. Concentrations of the active S-enantiomer in synovial fluid exceeded those of the R-enantiomer at all times in all patients with the ratio of S to R concentrations being 2.1 +/- 0.3 (mean +/- SE). Synovial fluid concentrations fluctuated much less than in plasma and exceeded plasma concentrations from 5.4 +/- 0.3 hours for R-ibuprofen and 5.5 +/- 0.6 hours for S-ibuprofen. Pharmacokinetic analysis suggested that, although the enantiomers diffuse into synovial fluid primarily in the unbound form, there may be significant diffusion of the enantiomers out of synovial fluid in the protein-bound form in some patients. Interpatient differences in the disposition of the enantiomers of ibuprofen in synovial fluid were evident and may contribute to the interindividual variability in response to treatment with ibuprofen.
Day
R O
RO
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, NSW, Australia.
Williams
K M
KM
Graham
G G
GG
Lee
E J
EJ
Knihinicki
R D
RD
Champion
G D
GD
D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013237:Stereoisomerism; D013582:Synovial Fluid / Q000378:metabolism*
D007052:Ibuprofen