{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:22:34Z","timestamp":1785507754632,"version":"3.56.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The drug interaction potential of enarodustat (doses: 25, 50\u00a0mg) on the activity of cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 was evaluated after once\u2010daily administration for 15 days in a phase 1 multiple\u2010ascending\u2010dose study in healthy subjects. Probe substrates specific for the enzymes, i.e.,\u00a0caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4), were administered orally as a cocktail with (day\u00a015) and without (day \u22123) enarodustat. Drug interaction was based on geometric mean maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2010time curve from the time of dosing to infinity (AUC<jats:sub>inf<\/jats:sub>) ratios (day 15\/day \u22123) for CYP1A2, 2C9, 2C19, 2D6, 3A4, and urinary excretion of dextromethorphan metabolite dextrorphan for CYP2D6. At the 2 enarodustat doses, for caffeine, the geometric mean ratios (range) for C<jats:sub>max<\/jats:sub> and AUC<jats:sub>inf<\/jats:sub> were 0.99\u20131.06 and 1.61\u20131.63, respectively. The ratios for peak concentrations and total exposures were 0.98\u20131.07 and 0.71\u20131.78 for tolbutamide and omeprazole, respectively. For dextrorphan the C<jats:sub>max<\/jats:sub> and AUC<jats:sub>inf<\/jats:sub> ratios were 0.83\u20130.90 and 1.02\u20131.04, respectively. The mean dextrorphan cumulative amount excreted into the urine from the time of dosing to 24 hours values on day \u22123 and day 15 were 8.25 mg and 8.20 mg at the lower dose, and 9.40 mg and 9.51 mg at the higher dose. The ratios for midazolam C<jats:sub>max<\/jats:sub> and AUC<jats:sub>inf<\/jats:sub> were 1.42\u20131.63. Overall, there was a lack of enarodustat dose dependency regarding the geometric mean ratios and 90% confidence intervals and urinary excretion of dextrorphan. There were some cases where the 90% confidence intervals at the 2 enarodustat doses were outside the 0.80\u20131.25 range, but changes in the geometric mean ratios were all &lt;2\u2010fold.<\/jats:p>","DOI":"10.1002\/cpdd.1263","type":"journal-article","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T05:30:36Z","timestamp":1685770236000},"page":"667-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Drug\u2013Drug Interaction Potential of Enarodustat (JTZ\u2010951) Using a Cytochrome P450 Probe Cocktail"],"prefix":"10.1002","volume":"12","author":[{"given":"Sudhakar M.","family":"Pai","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Akros Pharma, Inc.  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