Ibuprofen enantiomers and lipid metabolism.
Recent findings concerning the mechanism of the chiral inversion of "profens" have given a better understanding of the ways in which profens interact with lipid biochemistry. This study presents investigations and findings concerning the influence of coenzyme-A (CoA) levels on the chiral inversion of ibuprofen. Measurement of intracellular coenzyme-A levels in isolated rat hepatocytes revealed that R-ibuprofen transiently reduced coenzyme-A levels, whereas S-ibuprofen had no effect. Other experiments were performed with rat hepatocyte suspensions, including tests with various concentrations of clofibric acid added to incubates. Results showed that both clofibric acid pretreatment and its presence in the perfusion medium increases the chiral inversion of R-ibuprofen. These results confirm a metabolic interaction between ibuprofen and clofibric acid. Clinical studies are continuing to determine whether this metabolic interaction has toxicologic consequences.
Mayer
J M
JM
Institute of Medical Chemistry, School of Pharmacy, University of Lausanne, Switzerland.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D002995:Clofibric Acid / Q000494:pharmacology; D003065:Coenzyme A / Q000032:analysis; D007052:Ibuprofen / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002995:Clofibric Acid; D003065:Coenzyme A; D007052:Ibuprofen