{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:45:03Z","timestamp":1772750703483,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"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":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a selective and potent inhibitor targeting the isocitrate dehydrogenase\u20102 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 probe drug), midazolam (CYP3A4 probe drug), omeprazole (CYP2C19 probe drug), and pioglitazone (CYP2C8 probe drug), in patients with AML or myelodysplastic syndrome. Results showed that following the co\u2010administration of enasidenib (100 mg, once daily) for 28 days, the PK parameters AUC<jats:sub>(0\u2010\u221e)<\/jats:sub> and C<jats:sub>max<\/jats:sub> of dextromethorphan increased by 1.37 (90% confidence interval (CI): 0.96, 1.96) and 1.24 (90% CI: 0.94, 1.65)\u2010fold, respectively, compared to dextromethorphan alone. For flurbiprofen, these parameters increased by 1.14 (90%CI: 1.01, 1.29) and 0.97 (90% CI 0.86, 1.08)\u2010fold, respectively, when compared to flurbiprofen alone. Conversely, midazolam exhibited decreases to 0.57 (90% CI 0.34, 0.97) and 0.77 (90% CI 0.39, 1.53)\u2010fold, respectively, in comparison to midazolam alone. The parameters for omeprazole increased by 1.86 (90% CI: 1.33, 2.60) and 1.47 (0.93, 2.31)\u2010fold, respectively, compared to omeprazole alone, while those for pioglitazone decreased to 0.80 (90% CI: 0.62, 1.03) and 0.87 (90% CI: 0.65, 1.16)\u2010fold, respectively, in comparison to pioglitazone alone. These findings provide valuable insights into dose recommendations concerning drugs acting as substrates of CYP2D6, CYP2C9, CYP3A4, CYP2C19, and CYP2C8 when administered concurrently with enasidenib.<\/jats:p>","DOI":"10.1002\/jcph.2436","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T08:09:58Z","timestamp":1712045398000},"page":"984-992","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessment of CYP\u2010Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome"],"prefix":"10.1002","volume":"64","author":[{"given":"Yiming","family":"Cheng","sequence":"first","affiliation":[{"name":"Clinical Pharmacology, Pharmacometrics &amp; Bioanalysis Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacometrics &amp; Bioanalysis Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atalanta","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Global Biometrics and Data Sciences Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Pu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacometrics &amp; Bioanalysis Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas N","family":"Carayannopoulos","sequence":"additional","affiliation":[{"name":"Global Drug Development Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacometrics &amp; Bioanalysis Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0536"},{"issue":"4","key":"e_1_2_10_3_1","first-page":"247","article-title":"Enasidenib for patients with relapsed acute myeloid leukemia and the IDH2 mutation","volume":"16","author":"DiNardo C","year":"2018","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2018.1477585"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.11.015"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231677"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-04-779405"},{"key":"e_1_2_10_8_1","unstructured":"IDHIFA\u00ae (enasidenib). 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