The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat. |
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Authors: | B Zhao G Geisslinger I Hall R O Day K M Williams |
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Affiliation: | Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia. |
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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 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. |
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Keywords: | 2-arylpropionic acids nonsteroidal antiinflammatory drugs stereoselective coenzyme A thioesters chiral inversion oxidative phosphorylation |
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