{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:41:57Z","timestamp":1775886117699,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"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":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cytomegalovirus (CMV) viral terminase inhibitor letermovir is indicated for prevention of CMV infection in CMV\u2010seropositive allogeneic hematopoietic stem cell transplant recipients. In this analysis, functional variants in solute carrier organic anion transporter family member 1B1 (<jats:italic>SLCO1B1<\/jats:italic>), uridine diphosphate\u2010glucuronosyltransferase 1A1 (<jats:italic>UGT1A1<\/jats:italic>), and breast cancer resistance protein (<jats:italic>BCRP<\/jats:italic>) were assessed for effects on letermovir pharmacokinetics (PK) using pooled genetic information from 296 participants in 12 phase 1 studies. Letermovir area under the plasma concentration\u2010time curve (AUC) was increased in carriers of the <jats:italic>SLCO1B1<\/jats:italic> variant rs4149056 C allele relative to noncarriers with a geometric mean ratio (GMR) of 1.18 (95% confidence interval [CI], 1.06\u20131.30) for carriers of 1 copy and 1.42 (1.10\u20131.84) for carriers of 2 copies of the risk allele C compared with noncarriers. The <jats:italic>SLCO1B1<\/jats:italic> variant rs4149032 T allele was associated with a decrease in letermovir AUC with GMR (95%CI) of 0.93 (0.85\u20131.02) and 0.82 (0.73\u20130.92) for carriers of 1 and 2 copies of the risk allele\u00a0T, respectively, compared with noncarriers. The <jats:italic>UGT1A1*6<\/jats:italic> variant rs4148323 A allele was present predominantly in Asian participants and was associated with an increase in letermovir AUC compared with noncarriers (GMR, 1.36; 95%CI, 1. 1.07\u20131.74). <jats:italic>SLCO1B1<\/jats:italic> variant rs2306283, <jats:italic>UGT1A1*28<\/jats:italic> TA promoter repeat, and <jats:italic>BCRP<\/jats:italic> variant rs2231142 had no effect on letermovir PK. Together, these data suggest that variants of enzymes and transporters that are involved in the disposition of letermovir in vitro may account for some variability in letermovir PK, but do not affect exposure to a clinically relevant extent.<\/jats:p>","DOI":"10.1002\/jcph.1420","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T16:03:49Z","timestamp":1556208229000},"page":"1236-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacogenetic Analysis of <i>OATP1B1<\/i>, <i>UGT1A1<\/i>, and <i>BCRP<\/i> Variants in Relation to the Pharmacokinetics of Letermovir in Previously Conducted Clinical Studies"],"prefix":"10.1002","volume":"59","author":[{"given":"Julie","family":"Kobie","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zifang","family":"Guo","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn R.","family":"Cho","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Menzel","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline B.","family":"McCrea","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  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