{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T20:05:05Z","timestamp":1783800305403,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Letermovir, a cytomegalovirus (CMV) DNA terminase complex inhibitor, is a substrate of ABCB1 (P\u2010glycoprotein; P\u2010gp), organic anion transporting polypeptide (OATP)1B1\/3, UDP\u2010glucuronosyltransferase (UGT)1A1, UGT1A3 and possibly ABCG2 (breast cancer resistance protein; BCRP). A study was conducted to evaluate the effects of itraconazole, a prototypic ABCB1\/ABCG2 inhibitor, on letermovir pharmacokinetics (PK) and the effects of letermovir on itraconazole PK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In an open\u2010label, fixed\u2010sequence study in 14 healthy participants, 200\u2009mg oral itraconazole was administered once daily for 4\u2009days. Following a 10\u2010day washout, 480\u2009mg oral letermovir was administered once daily for 14\u2009days (Days 1\u201314) and then coadministered with 200\u2009mg itraconazole once daily for 4 days (Days 15\u201318). Intensive PK sampling was performed for letermovir and itraconazole. PK and safety were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Letermovir geometric mean ratio (GMR; 90% confidence interval [CI]) for area under the concentration\u2013time curve from time 0 to 24\u2009h (AUC<jats:sub>0\u201324<\/jats:sub>) was 1.33 (1.17, 1.51) and for maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) was 1.21 (1.05, 1.39) following administration with\/without itraconazole. Itraconazole GMR (90% CI) for AUC<jats:sub>0\u201324<\/jats:sub> was 0.76 (0.71, 0.81) and for <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> was 0.84 (0.76, 0.92) following administration with\/without letermovir. Coadministration of letermovir with itraconazole was generally well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The increase in letermovir exposure with coadministration of itraconazole is likely predominantly due to inhibition of intestinal ABCB1 and potentially ABCG2 transport. The mechanism for the decrease in itraconazole exposure is unknown. The modest changes in letermovir and itraconazole PK are not considered clinically meaningful.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15677","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T02:23:45Z","timestamp":1675131825000},"page":"2122-2130","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of the inhibitory effects of itraconazole on letermovir"],"prefix":"10.1111","volume":"89","author":[{"given":"Jacqueline B.","family":"McCrea","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Menzel","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Fancourt","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Witter","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,12]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Merck Sharp & Dohme Corp. Whitehouse Station NJ USA. PREVYMIS\u2122 (letermovir) Prescribing Information.https:\/\/www.merck.com\/product\/usa\/pi_circulars\/p\/prevymis\/prevymis_pi.pdf. Published 2020. Accessed January 18 2021."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05908\u201011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05265\u201011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706640"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1423"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12593"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1081"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200222666210223112826"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1420"},{"key":"e_1_2_10_11_1","unstructured":"Janssen Pharmaceuticals Inc.SPORANOX\u00ae (itraconazole) Prescribing Information.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/020657s037lbl.pdf. Published2019. Updated August 2022. 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