{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:14:15Z","timestamp":1780514055174,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T00:00:00Z","timestamp":1565049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Shire, a Takeda company"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Maribavir is an investigational drug being evaluated in transplant recipients with cytomegalovirus infection. To understand potential drug\u2010drug interactions, we examined the effects of multiple doses of maribavir on cytochrome P450 (CYP) 2D6 and P\u2010glycoprotein (P\u2010gp) activity using probe substrates in healthy volunteers. During this phase 1 open\u2010label study (NCT02775240), participants received the probe substrates digoxin (0.5 mg) and dextromethorphan (30 mg) before and after maribavir (400 mg twice daily for 8 days). Serial plasma samples were analyzed for digoxin, dextromethorpha, dextrorphan, and maribavir concentrations. Pharmacokinetic parameters were calculated (noncompartmental analysis) and analyzed with a linear mixed\u2010effects model for treatment comparison to estimate geometric mean ratios (GMRs) and 90% confidence intervals (CIs). CYP2D6 polymorphisms were genotyped using polymerase chain reaction. Overall, 17 of 18 participants (94.4%) completed the study. All participants were genotyped as CYP2D6 intermediate\/extensive metabolizers. GMR (90%CI) of digoxin C<jats:sub>max<\/jats:sub>, AUC<jats:sub>last<\/jats:sub>, and AUC<jats:sub>0\u2010\u221e<\/jats:sub> with and without maribavir was 1.257 (1.139\u20101.387), 1.187 (1.088\u20101.296), and 1.217 (1.110\u20101.335), respectively, outside the \u201cno\u2010effect\u201d window (0.8\u20101.25). GMR (90%CI) of dextromethorphan AUC<jats:sub>last<\/jats:sub> and AUC<jats:sub>last<\/jats:sub> ratio of dextromethorphan\/dextrorphan were 0.877 (0.692\u20101.112) and 0.901 (0.717\u20101.133), respectively, marginally outside the no\u2010effect window, although large variability was observed in these pharmacokinetic parameters. Pharmacokinetic parameters of dextrorphan were unaffected. Maribavir inhibited P\u2010gp activity but did not affect CYP2D6 activity. Maribavir's effect on the pharmacokinetics of P\u2010gp substrates should be evaluated individually, and caution should be exercised with P\u2010gp substrates with narrow therapeutic windows.<\/jats:p>","DOI":"10.1002\/jcph.1504","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T10:59:14Z","timestamp":1565089154000},"page":"96-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Maribavir on P\u2010Glycoprotein and CYP2D6 in Healthy Volunteers"],"prefix":"10.1002","volume":"60","author":[{"given":"Ivy H.","family":"Song","sequence":"first","affiliation":[{"name":"Shire, a Takeda company  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Ilic","sequence":"additional","affiliation":[{"name":"Shire, a Takeda company  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Murphy","sequence":"additional","affiliation":[{"name":"Shire, a Takeda company  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Lasseter","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology of Miami Inc.  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Martin","sequence":"additional","affiliation":[{"name":"Shire, a Takeda company  Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679639"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12732"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2015(07)09"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0943-1"},{"key":"e_1_2_11_6_1","unstructured":"Accessdata. Ganciclovir. Highlights of prescribing information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209347lbl.pdf. Accessed April 4 2019."},{"key":"e_1_2_11_7_1","unstructured":"Accessdata. Valcyte. 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