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Stereoselective Disposition of Etodolac Enantiomers in Synovial Fluid
Author(s) -
Brocks Dion R.,
Jamali Fakhreddin,
Russell Anthony S.
Publication year - 1991
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1991.tb03770.x
Subject(s) - etodolac , chemistry , synovial fluid , pharmacology , enantiomer , stereoselectivity , chromatography , medicine , stereochemistry , biochemistry , osteoarthritis , alternative medicine , pathology , catalysis
The synovial fluid (SF) uptake of the chiral nonsteroidal anti‐inflammatory drug, etodolac, was studied in six arthritic patients, 2 hours (n = 1) or 12 hours (n = 5) after a single 200 mg dose of racemate. Marked stereoselectivity was seen in both SF and plasma; concentrations of pharmacologically inactive R‐etodolac were up to 10‐fold greater than active S‐etodolac. Concentrations of S‐etodolac were greater in SF than in plasma (SF:plasma ratio = 1.98 ± 0.8): No such difference was seen for R‐etodolac (SF:plasma = 0.91 ± 0.3). Considerable concentrations of conjugated enantiomers were present in SF . In vitro equilibrium dialysis studies in drug‐spiked samples showed that the unbound fraction of both enantiomers in SF was greater than in plasma; both fluids bound R more extensively than S etodolac. Therapeutically active S‐etodolac has greater concentrations in synovial fluid than plasma during the post‐distributive phase, which may be of possible clinical relevance .