{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T02:09:51Z","timestamp":1775268591703,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"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":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rolapitant (Varubi) is a neurokinin\u20101 receptor antagonist approved for the prevention of chemotherapy\u2010induced nausea and vomiting. Rolapitant is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. Unlike other neurokinin\u20101 receptor antagonists, rolapitant is neither an inhibitor nor an inducer of CYP3A4 in vitro. The objective of this analysis was to examine the pharmacokinetics of rolapitant in healthy subjects and assess drug\u2010drug interactions between rolapitant and midazolam (a CYP3A substrate), ketoconazole (a CYP3A inhibitor), or rifampin (a CYP3A4 inducer). Three phase 1, open\u2010label, drug\u2010drug interaction studies were conducted to examine the pharmacokinetic interactions of orally administered rolapitant with midazolam, rolapitant with ketoconazole, and rolapitant with rifampin. The pharmacokinetic profiles of midazolam and 1\u2010hydroxy midazolam metabolites were essentially unchanged when coadministered with rolapitant, indicating the lack of a clinically relevant inhibition or induction of CYP3A by rolapitant. Coadministration of ketoconazole with rolapitant had no effects on rolapitant maximum concentration and resulted in an approximately 20% increase in the area under the concentration\u2010time curve of rolapitant, suggesting that strong CYP3A inhibitors have minimal inhibitory effects on rolapitant exposure. Repeated administrations of rifampin appeared to reduce rolapitant exposure, resulting in a 33% decrease in maximum concentration and 87% decrease in area under the concentration\u2010time curve from time zero to infinity. Coadministration of rolapitant did not affect the exposure of midazolam. Rifampin coadministration resulted in lower concentrations of rolapitant, and ketoconazole coadministration had no or minimal effects on rolapitant exposure. Rolapitant was safe and well tolerated when coadministered with ketoconazole, rifampin, or midazolam. No new safety signals were reported compared with previous studies of rolapitant.<\/jats:p>","DOI":"10.1002\/jcph.1339","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T10:55:52Z","timestamp":1542106552000},"page":"488-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic Interactions of Rolapitant With Cytochrome P450 3A Substrates in Healthy Subjects"],"prefix":"10.1002","volume":"59","author":[{"given":"Xiaodong","family":"Wang","sequence":"first","affiliation":[{"name":"TESARO, Inc. Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"TESARO, Inc. Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujata","family":"Arora","sequence":"additional","affiliation":[{"name":"TESARO, Inc. 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Waltham MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.09.073"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0706547"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.03.021"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-015-2738-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.637"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00035-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00034-0"},{"key":"e_1_2_9_10_1","unstructured":"Varubi\u00ae (rolapitant) prescribing information.Waltham MA:Tesaro Inc.; (2018)https:\/\/www.varubirx.com\/application\/files\/9315\/2156\/0391\/Varubi_tabs_and_inj_emul_USPI_Clean_March_2018.pdfAccessed September 6 2018."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0724-6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602539709037591"},{"issue":"21","key":"e_1_2_9_13_1","first-page":"5121","article-title":"Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions","volume":"53","author":"Zhou\u2010Pan XR","year":"1993","journal-title":"Cancer Res"},{"issue":"6","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0090-9556(24)15302-0","article-title":"Development of a substrate\u2010activity based approach to identify the major human liver P\u2010450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA\u2010expressed activities and liver microsomal P\u2010450 profiles","volume":"27","author":"Roy P","year":"1999","journal-title":"Drug Metab Dispos"},{"issue":"3","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/S0022-3565(24)37724-9","article-title":"A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes","volume":"286","author":"Kawashiro T","year":"1998","journal-title":"J\u00a0Pharmacol Exp Ther"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/15.12.2715"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1887"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1388-1"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.9.985"},{"issue":"1","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/S0022-3565(25)22379-5","article-title":"Interindividual variations in human liver cytochrome P\u2010450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians","volume":"270","author":"Shimada T","year":"1994","journal-title":"J\u00a0Pharmacol Exp Ther"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-013-1855-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00123-1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007300807"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010387792"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270003262950"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008331196"},{"key":"e_1_2_9_28_1","article-title":"Absorption, metabolism, and excretion of the antiemetic rolapitant, a selective neurokinin\u20101 receptor antagonist, in healthy male subjects [published online ahead of print July 21, 2018","author":"Zhang ZY","journal-title":"Inv New Drugs"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-013-1857-9"},{"key":"e_1_2_9_30_1","unstructured":"EMEND (aprepitant) capsules for oral use EMEND (aprepitant) for oral suspension. 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