The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat.
The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta-oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism.
Zhao
B
B
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.
Geisslinger
G
G
Hall
I
I
Day
R O
RO
Williams
K M
KM
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D005480:Flurbiprofen / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D010169:Palmitic Acids; D002245:Carbon Dioxide; D019308:Palmitic Acid; D005480:Flurbiprofen; D007052:Ibuprofen