Fusidic Acid Inhibits Hepatic Transporters and Metabolic Enzymes: Potential Cause of Clinical Drug-Drug Interaction Observed with Statin Coadministration.

ABSTRACT: Fusidic acid (FA), which was approved in the 1960s in many European and Asian countries, has gained renewed interest due to its continued effectiveness against methicillin-resistant Staphylococcus aureus As rhabdomyolysis has been reported upon coadministration of FA with statins, we aimed to elucidate the underlying molecular mechanisms that contribute to FA-statin drug-drug interactions. Because of the association between rhabdomyolysis and increased exposure to statins, we investigated if cytochrome P450 (CYP) enzymes and transporters involved in the disposition of various statins are inhibited by FA. FA was found to inhibit BCRP and OATP1B1 but not P-gp. In overexpressing cell systems, FA inhibited BCRP-mediated efflux (50% inhibitory concentration [IC50], ∼50 to 110 μM) and OATP1B1-me

SUBMITTER: Gupta A 

PROVIDER: S-EPMC5038258 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature