Stereochemical pharmacokinetics of the 2-arylpropionic acid non-steroidal antiinflammatory drug flunoxaprofen in rats and in man.
Stereospecific serum assays of the non-steroidal antiinflammatory drug flunoxaprofen (S(+)-2-(4-fluorophenyl)-a-methyl-5-benzoxazoleacetic acid, Priaxim) were performed in rats after the oral administration of 10 mg/kg b.w. of the different enantiomeric forms of the drug or of the racemate in order to establish the occurrence and the rate of biotransformation of R(-)-flunoxaprofen to the S(+)-enantiomer, which is the pharmacologically active form. Preliminary observations of the enantiomeric blood levels were also made in man after a single oral dose (100 mg) of R(-)-flunoxaprofen or of the racemate. Blood was withdrawn at different time intervals up to 120 h in rats and up to 48 h in man and serum levels of flunoxaprofen enantiomers were determined by a HPLC method. The results obtained in the rat show that S(+)-flunoxaprofen serum levels following the administration of a single oral dose of flunoxaprofen reach about the same values (between 24 and 30 micrograms/ml at 18 h) whichever form was dosed (i.e. 10 mg/kg b.w. of S(+)- or R(+)-, or 5 mg/kg b.w. of S(+)- as the racemate). On the contrary, R(-)-flunoxaprofen serum concentrations fall to values lower than 5 micrograms/ml either after the administration of 10 mg/kg R(-)- or of 5 mg/kg R(-)- as the racemate; these serum R(-)-flunoxaprofen values are close to those observed after the administration of S(+)-flunoxaprofen which contains 5% R(-)- as an impurity (i.e. 0.5 mg/kg b.w.).(ABSTRACT TRUNCATED AT 250 WORDS)
Pedrazzini
S
S
Research & Development Department, Ravizza S.p.A. Muggiò/Milan, Italy.
De Angelis
M
M
Muciaccia
W Z
WZ
Sacchi
C
C
Forgione
A
A
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001583:Benzoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D006207:Half-Life; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; C045356:flunoxaprofen