{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:31:50Z","timestamp":1770751910730,"version":"3.50.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T00:00:00Z","timestamp":1372118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"name":"ARIAD Pharmaceuticals, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Ponatinib is a BCR\u2010ABL tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome\u2013positive acute lymphoblastic leukemia in patients resistant or intolerant to prior TKIs. In vitro studies suggested that metabolism of ponatinib is partially mediated by CYP3A4. The effects of CYP3A4 inhibition on the pharmacokinetics of ponatinib and its CYP3A4\u2010mediated metabolite, AP24567, were evaluated in a single\u2010center, randomized, two\u2010period, two\u2010sequence crossover study in healthy volunteers. Subjects (N\u2009=\u200922) received two single doses (orally) of ponatinib 15\u2009mg, once given alone and once coadministered with daily (5 days) ketoconazole 400\u2009mg, a CYP3A4 inhibitor. Ponatinib plus ketoconazole increased ponatinib maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the concentration\u2013time curve (AUC) compared with ponatinib alone. The estimated mean ratios for AUC<jats:sub>0\u2013\u221e<\/jats:sub>, AUC<jats:sub>0\u2013t<\/jats:sub>, and C<jats:sub>max<\/jats:sub> indicated increased exposures to ponatinib of 78%, 70%, and 47%, respectively; exposure to AP24567 decreased by 71%. Exposure to AP24567 was marginal after ponatinib alone (no more than 4% of the exposure to ponatinib). These results suggest that caution should be exercised with the concurrent use of ponatinib and strong CYP3A4 inhibitors and that a ponatinib dose decrease to 30\u2009mg daily, from the 45\u2009mg daily starting dose, could be considered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.109","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T16:20:58Z","timestamp":1372177258000},"page":"974-981","source":"Crossref","is-referenced-by-count":54,"title":["Effects of Ketoconazole on the Pharmacokinetics of Ponatinib in Healthy Subjects"],"prefix":"10.1002","volume":"53","author":[{"given":"Narayana I.","family":"Narasimhan","sequence":"first","affiliation":[{"name":"ARIAD Pharmaceuticals, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Dorer","sequence":"additional","affiliation":[{"name":"ARIAD Pharmaceuticals, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Niland","sequence":"additional","affiliation":[{"name":"ARIAD Pharmaceuticals, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Haluska","sequence":"additional","affiliation":[{"name":"ARIAD Pharmaceuticals, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl","family":"Sonnichsen","sequence":"additional","affiliation":[{"name":"ARIAD Pharmaceuticals, Inc. 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