{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:49:04Z","timestamp":1773312544854,"version":"3.50.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            . 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 [IC\n            <jats:sub>50<\/jats:sub>\n            ], \u223c50 to 110 \u03bcM) and OATP1B1-mediated uptake (IC\n            <jats:sub>50<\/jats:sub>\n            , \u223c4 to 35 \u03bcM) of statins at clinically relevant concentrations achievable in the intestine and liver (based on a 550-mg oral dose of FA, the expected maximum theoretical gastrointestinal concentration is \u223c4 mM, and the maximum total or unbound concentration in the inlet to the liver was reported to be up to 223 \u03bcM or 11 \u03bcM, respectively, upon multiple dosing). Similarly, FA inhibited metabolism of statins in human liver microsomes (IC\n            <jats:sub>50<\/jats:sub>\n            , \u223c17 to 195 \u03bcM). These data suggest that FA inhibits at least 3 major dispositional pathways (BCRP, OATP1B1, and CYP3A) and thus affects the clearance of several statins. We confirmed that FA is eliminated via phase 1 metabolism (primarily via CYP3A); however, there is also some phase 2 metabolism (mediated primarily by UGT1A1). Taken together, these data provide evidence for molecular mechanisms that may explain the occurrence of rhabdomyolysis when FA is administered with statins.\n          <\/jats:p>","DOI":"10.1128\/aac.01335-16","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:33:19Z","timestamp":1469500399000},"page":"5986-5994","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Fusidic Acid Inhibits Hepatic Transporters and Metabolic Enzymes: Potential Cause of Clinical Drug-Drug Interaction Observed with Statin Coadministration"],"prefix":"10.1128","volume":"60","author":[{"given":"Anshul","family":"Gupta","sequence":"first","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics, Infection Innovative Medicines Unit, AstraZeneca R&amp;D Boston, Waltham, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer J.","family":"Harris","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics, Infection Innovative Medicines Unit, AstraZeneca R&amp;D Boston, Waltham, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianrong","family":"Lin","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Bulgarelli","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce K.","family":"Birmingham","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals LP, Wilmington, Delaware, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott W.","family":"Grimm","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Pharmacokinetics, Infection Innovative Medicines Unit, AstraZeneca R&amp;D Boston, Waltham, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/499819"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq067"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6562"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00207-2.x"},{"key":"e_1_3_3_6_2","volume-title":"Fucidin suspension","author":"Leo Laboratories Ltd","year":"2013","unstructured":"Leo Laboratories Ltd. 2013. 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