The effect of the enantiomers of ibuprofen and flurbiprofen on the β‐oxidation of palmitate in the rat

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Abstract
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 β‐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 β‐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 β‐oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo β‐oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A‐dependent mechanism.