{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T18:33:52Z","timestamp":1732041232691},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"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":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Letermovir (MK\u20108228\/AIC246) is a cytomegalovirus (CMV) DNA terminase complex inhibitor for CMV prophylaxis in adult patients undergoing hematopoietic stem cell transplant. It is cytochrome P450 (CYP) 3A inhibitor and inhibits organic anion transporting polypeptide 1B1\/3 and breast cancer resistance protein transporters. Atorvastatin (ATV), a commonly used treatment for hypercholesterolemia, is a substrate of organic anion transporting polypeptide 1B1, potentially breast cancer resistance protein, and CYP3A. As letermovir may be coadministered with ATV, the effect of multiple\u2010dose letermovir 480\u00a0mg once daily on the pharmacokinetics of single\u2010dose ATV 20\u00a0mg and its metabolites (ortho\u2010hydroxyatorvastatin [o\u2010OH\u2010ATV] and para\u2010hydroxyatorvastatin [p\u2010OH\u2010ATV]) was evaluated in an open\u2010label trial in healthy female adults (N = 14). ATV area under the plasma concentration\u2013time curve from time 0 to infinity and maximum plasma concentration (C<jats:sub>max<\/jats:sub>) increased \u22483\u2010fold with letermovir coadministration. The time to ATV C<jats:sub>max<\/jats:sub> also increased, while apparent clearance decreased. The exposures of o\u2010OH\u2010ATV and p\u2010OH\u2010ATV were comparable in the presence versus absence of letermovir; however, o\u2010OH\u2010ATV C<jats:sub>max<\/jats:sub> decreased by 60% with coadministration, while p\u2010OH\u2010ATV C<jats:sub>max<\/jats:sub> was similar. Due to the increase in ATV exposure with letermovir coadministration, statin\u2010associated adverse events such as myopathy should be closely monitored following coadministration. The dose of ATV should not exceed 20\u00a0mg daily when coadministered with letermovir.<\/jats:p>","DOI":"10.1002\/cpdd.1071","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T18:56:20Z","timestamp":1644864980000},"page":"420-428","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Drug\u2010Drug Interaction of Letermovir and Atorvastatin in Healthy Participants"],"prefix":"10.1002","volume":"11","author":[{"given":"Jacqueline B.","family":"McCrea","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Menzel","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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