Ibuprofen metabolic pathways

Chiral inversion is a unique metabolic pathway that is known to influence the plasma concentrations of some of the 2-APAs, such as ibuprofen and fenoprofen, but less so for other drugs such as ketoprofen and flurbiprofen (see Chap. 8). In addition to chiral inversion, these drugs are subject to drug-dependent stereoselectivity in microsomal oxidation and/or glucuronidation. 

It also appears that tiaprofenic acid, an NSAID that also undergoes inversion in rats, is not a substrate for purified microsomal rat liver long-chain acyl-CoA synthetase for which R-ibuprofen is a substrate [25]. This data may suggest that metabolic pathways involved in the inversion of tiaprofenic acid and possibly other 2-APA NSAIDs are different from those known for R-ibuprofen. It has been recently reported that in both an in vitro cell-free system and in rat liver homogenates the chiral inversion of ibuprofen was apparent when both CoA and ATP were present however, the NSAID KE-748 was not inverted [26]. To induce hepatic microsomal and outer mitochondrial long-chain fatty acid CoA ligase, rats were treated with clofibric acid [27]. Whereas chiral inversion of ibuprofen was enhanced significantly compared to controls, this was not the case for R(—)-KE-748. 

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