Stereospecific disposition of flunoxaprofen enantiomers in human beings.
The absorption and disposition kinetics of the enantiomers of the nonsteroidal antiinflammatory drug flunoxaprofen were studied in six healthy volunteers after oral administration of either R,S(+/-)-flunoxaprofen or R(-)-flunoxaprofen. The apparent values of the volume of distribution and systemic clearance of the S(+)-enantiomer were significantly lower than those of the R(-)-enantiomer. There was no significant difference in the absorption and elimination half-lives between the two isomers. The S(+)- to R(-)-isomer plasma concentration ratio increased with time with an apparent inversion half-time of about 50 h. This observation suggests metabolic inversion of R(-)- to S(+)-enantiomer, although the possibilities of stereoselective bioavailability or interaction between the two isomers can not be excluded.
Palatini
P
P
Department of Pharmacology, University of Padua, Italy.
Montanari
G
G
Perosa
A
A
Forgione
A
A
Pedrazzini
S
S
Furlanut
M
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D001583:Benzoxazoles / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; C045356:flunoxaprofen