{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:19:44Z","timestamp":1791289184602,"version":"4.3.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T00:00:00Z","timestamp":1536019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nilotinib, an oral inhibitor of the tyrosine kinase activity of Abelson protein, is approved for the treatment of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase and patients with CML in chronic phase or accelerated phase resistant or intolerant to prior therapies. This review describes the pharmacokinetic and pharmacodynamic data of nilotinib in patients with CML and in healthy volunteers. Nilotinib is rapidly absorbed, with a peak serum concentration approximately 3 hours after dosing. The area under the plasma drug concentration\u2010time curve over 24 hours and the peak serum concentration of nilotinib were dose proportional from 50\u2010400 mg once daily. The metabolism of nilotinib is primarily via hepatic cytochrome P450 (CYP) 3A4 according to in vitro studies. In the clinical setting, exposure to nilotinib was significantly reduced by the induction of CYP3A4 with rifampicin and significantly increased by the inhibition of CYP3A with ketoconazole. Additionally, nilotinib is a competitive inhibitor of CYP3A4\/5, CYP2C8, CYP2C9, CYP2D6, and uridine diphosphate glucuronosyltransferase 1A1. The bioavailability of nilotinib is increased by up to 82% when given with a high\u2010fat meal compared with fasted state. There is a positive correlation between the occurrences of all\u2010grade total bilirubin elevations and the steady\u2010state nilotinib trough concentrations. Fredericia method corrected QT interval change from baseline was observed to have a correlation with nilotinib exposure. No significant relationship between nilotinib exposure and major molecular response at 12 months was seen at therapeutic doses of nilotinib 300\u2013400 mg, probably due to the narrow range of the doses investigated.<\/jats:p>","DOI":"10.1002\/jcph.1312","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T15:33:11Z","timestamp":1536075191000},"page":"1533-1540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Clinical Pharmacokinetic and Pharmacodynamic Overview of Nilotinib, a Selective Tyrosine Kinase Inhibitor"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2023-7198","authenticated-orcid":false,"given":"Xianbin","family":"Tian","sequence":"first","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hefei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tycho","family":"Heimbach","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Handan","family":"He","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aby","family":"Buchbinder","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Aghoghovbia","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Hourcade\u2010Potelleret","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  One Health Plaza East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907153410306"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199904293401706"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"e_1_2_11_5_1","article-title":"Chronic myeloid leukemia","author":"Cortes JE","year":"2017","journal-title":"Cancer Management"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2009.07.007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2011.576238"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24536"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.049759"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.5"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8899"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-739086"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21299"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.01.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2601"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0259"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.08.026"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603170"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.11.008"},{"key":"e_1_2_11_20_1","unstructured":"Novartis Pharmaceuticals Corporation Tasigna (Nilotinib) prescribing information.https:\/\/www.pharma.us.novartis.com\/product\/pi\/pdf\/tasigna.pdf. 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