{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:01:08Z","timestamp":1778814068611,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>In patients of all ages, metamizole is a frequently used analgesic. Recently, metamizole has been identified as an inducer of, among others, cytochrome P450 (CYP) 3A activity, but the time course of this interaction has not been evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using repeated oral microdoses (30\u2009\u03bcg) of the CYP3A index substrate midazolam, we assessed changes in midazolam pharmacokinetics (area under the concentration\u2013time curve from 2\u20134\u00a0h: AUC<jats:sub>2\u20134<\/jats:sub> and estimated partial metabolic clearance: eCl<jats:sub>met<\/jats:sub>) before, at steady\u2010state, and after discontinuation of 3\u00a0\u00d7\u20091000\u2009mg metamizole\/day orally for 8\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant changes in pharmacokinetic parameters were detected already 3\u2009days after start of metamizole treatment. At the steady\u2010state of enzyme induction, the geometric mean ratio of midazolam AUC<jats:sub>2\u20134<\/jats:sub> was substantially reduced to 0.18 (90% confidence interval: 0.14\u20130.24) with a corresponding 5.43\u2010fold (4.15\u20137.10) increase of eCl<jats:sub>met<\/jats:sub>. After discontinuation of metamizole, the changes slowly recovered, but were still significant at the end of the observation period on the fifth day after discontinuation of metamizole therapy (AUC<jats:sub>2\u20134<\/jats:sub> reduced to 0.50 [0.41\u20130.63] and eCl<jats:sub>met<\/jats:sub> 1.99\u2010fold increased [1.60\u20132.47, <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.05]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Metamizole acts as a strong inducer of CYP3A already few days after start of metamizole administration and, thus, should be avoided in patients using drugs with narrow therapeutic index and major clearance via CYP3A. If their administration is essential, close monitoring and dose adjustment of comedication should be performed as early as the first week after the initiation and after discontinuation of metamizole therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15720","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T09:42:56Z","timestamp":1679478176000},"page":"2458-2464","source":"Crossref","is-referenced-by-count":15,"title":["Time course of CYP3A activity during and after metamizole (dipyrone) in healthy volunteers"],"prefix":"10.1111","volume":"89","author":[{"given":"Mareile H.","family":"Breithaupt","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University Hospital  Im Neuenheimer Feld 410 69120 Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Krohmer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology 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