{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T13:16:30Z","timestamp":1717074990039},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"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":[[2024,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study evaluated drug\u2013drug interactions between the CYP3A4 inhibitor carotegrast methyl and the other CYP3A4 substrates, midazolam, atorvastatin and prednisolone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 88 healthy volunteers orally received carotegrast methyl 960\u2009mg 3 times daily for 14\u2009days. A single oral (5\u2009mg) or intravenous (0.017\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>) midazolam, oral (5\u2009mg) prednisolone or oral (10\u2009mg) atorvastatin was administered before, with and after carotegrast methyl treatment. When the 90% confidence interval (CI) for the geometric mean ratios of the pharmacokinetic (PK) parameters with coadministration with carotegrast methyl (Day 14) to those before carotegrast methyl administration was between 0.80 and 1.25, no PK interaction were deemed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010t<\/jats:sub> of oral midazolam before administration of carotegrast methyl were 30.9\u2009\u00b1\u20099.8\u2009ng\u2009mL<jats:sup>\u22121<\/jats:sup> and 74.5\u2009\u00b1\u200921.9\u2009ng\u2009h\u2009mL<jats:sup>\u22121<\/jats:sup>, respectively. The geometric mean ratio of the C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010t<\/jats:sub> of midazolam on Day 14 to those on Day \u22121 was 1.86 (90% CI, 1.64\u20132.11) and 3.07 (90% CI, 2.81\u20133.35), which did not fall within the range of 0.80\u20131.25, suggesting that carotegrast methyl had a PK interaction with midazolam. Similar PK interactions were found for intravenous midazolam and atorvastatin, but not for prednisolone. The inhibitory effect of carotegrast methyl on CYP3A4\u2010mediated metabolism of midazolam and atorvastatin had almost disappeared by 14\u2009days after the end of administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Carotegrast methyl was classified as a moderate CYP3A4 inhibitor in humans. 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