{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:30:08Z","timestamp":1777419008224,"version":"3.51.4"},"reference-count":26,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2007,4,1]],"date-time":"2007-04-01T00:00:00Z","timestamp":1175385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources:<\/jats:title>\n                    <jats:p>Literature was accessed using the MEDLINE database (1966\u2013February 2007). Search terms included metronidazole, cytochrome P450, CYP3A4, CYP3A5, drug interactions, and P-glycoprotein. References from pertinent articles, as well as from tertiary sources, were also considered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction:<\/jats:title>\n                    <jats:p>All articles identified from the data sources that were published in English were evaluated. Case reports and pharmacokinetic evaluations were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis:<\/jats:title>\n                    <jats:p>Elevated plasma concentrations and toxicities have been reported for a number of CYP3A substrates including amiodarone, carbamazepine, quinidine, tacrolimus, and cyclosporine when administered with metronidazole. This has led to the widespread belief that metronidazole is a significant inhibitor of CYP3A4. However, 4 pharmacokinetic studies conducted in humans showed that metronidazole did not increase plasma concentrations of the CYP3A substrates midazolam, erythromycin, cyclosporine, and alprazolam, thereby refuting the suggestion that metronidazole is a CYP3A4\/5 inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Drug interactions between metronidazole and certain CYP3A substrates do not appear to result from CYP3A4\/5 inhibition by metronidazole. Until any mechanism is identified by which metronidazole alters the disposition of certain CYP3A substrates, drug interactions with this agent should be assessed on a case-by-case basis, taking into account the safety index of the coadministered drug and the availability of equally effective substitutes for either metronidazole or the drug with which it putatively interacts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1h401","type":"journal-article","created":{"date-parts":[[2007,3,20]],"date-time":"2007-03-20T20:08:25Z","timestamp":1174421305000},"page":"653-658","source":"Crossref","is-referenced-by-count":22,"title":["Does Metronidazole Interact with CYP3A Substrates by Inhibiting Their Metabolism Through This Metabolic Pathway? Or Should Other Mechanisms Be Considered?"],"prefix":"10.1177","volume":"41","author":[{"given":"Rhonda","family":"Roedler","sequence":"first","affiliation":[{"name":"Peter Lougheed Centre, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda M","family":"Neuhauser","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott R","family":"Penzak","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics Research Laboratory, Clinical Center Pharmacy Department, National institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2007,4,1]]},"reference":[{"key":"bibr1-aph.1H401","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199754050-00003"},{"key":"bibr2-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197608122950702"},{"key":"bibr3-aph.1H401","first-page":"782","volume":"51","author":"Kazmier FJ","year":"1976","journal-title":"Mayo Clin Proc"},{"key":"bibr4-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1988.tb03139.x"},{"key":"bibr5-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.2005.09348.x"},{"key":"bibr6-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/14.2.521b"},{"key":"bibr7-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1177\/106002809402801118"},{"key":"bibr8-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1E399"},{"key":"bibr9-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1177\/106002809603000408"},{"key":"bibr10-aph.1H401","doi-asserted-by":"publisher","DOI":"10.1177\/106002808802200616"},{"key":"bibr11-aph.1H401","unstructured":"Lexi-Comp ONLINE, 1978\u20132006. http:\/\/online.lexi.com\/crlsql\/servlet\/crlonline (accessed 2007 Feb 20)."},{"key":"bibr12-aph.1H401","volume-title":"Micromedex Healthcare Series"},{"key":"bibr13-aph.1H401","unstructured":"Hansten PD Horn JT. 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