{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:52:23Z","timestamp":1790009543076,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T00:00:00Z","timestamp":1583712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007859","name":"University of Kansas","doi-asserted-by":"publisher","award":["KL2TR002367"],"award-info":[{"award-number":["KL2TR002367"]}],"id":[{"id":"10.13039\/100007859","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>This study investigated the impact of <jats:italic>SLCO1B1<\/jats:italic> genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8\u201321\u00a0years) with at least one allelic variant of <jats:italic>SLCO1B1<\/jats:italic> c.521T&gt;C (521TC, <jats:italic>n<\/jats:italic>\u00a0=\u00a013; 521CC, <jats:italic>n<\/jats:italic>\u00a0=\u00a02) and wild type controls (521TT, <jats:italic>n<\/jats:italic>\u00a0=\u00a013) completed a single oral dose pharmacokinetic study. The variability contributed by <jats:italic>SLCO1B1<\/jats:italic> c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration\u2010time curve from 0\u201324\u00a0hours (AUC<jats:sub>0\u201324<\/jats:sub>) was 1.4\u2010fold and 2.2\u2010fold higher in participants with c.521TC and c.521CC genotype compared 521TT participants, respectively. Interindividual variability of RVA exposure within <jats:italic>SLCO1B1<\/jats:italic> genotype groups exceeded the\u00a0~\u00a01.5\u2010fold to 2\u2010fold difference in mean RVA exposure observed among <jats:italic>SLCO1B1<\/jats:italic> genotype groups, suggesting that other factors also contribute to interindividual variability in the rosuvastatin dose\u2010exposure relationship. A multivariate model performed confirmed <jats:italic>SLCO1B1<\/jats:italic> c.521T&gt;C genotype as the primary factor contributing to RVA systemic exposure in this pediatric cohort, accounting for ~\u00a030% of the variability RVA AUC<jats:sub>0\u201324<\/jats:sub>. However, of the statins investigated to date in the pediatric population, RVA has the lowest magnitude of variability in systemic exposure.<\/jats:p>","DOI":"10.1111\/cts.12749","type":"journal-article","created":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T10:47:56Z","timestamp":1579949276000},"page":"628-637","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Impact of <i>SLCO1B1<\/i> Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia"],"prefix":"10.1111","volume":"13","author":[{"given":"Jonathan B.","family":"Wagner","sequence":"first","affiliation":[{"name":"Ward Family Heart Center Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Gaedigk","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Raghuveer","sequence":"additional","affiliation":[{"name":"Ward Family Heart Center Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent S.","family":"Staggs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"},{"name":"Health Services &amp; Outcomes Research Children\u2019s Mercy Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Van Haandel","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation Children\u2019s Mercy Kansas City Missouri USA"},{"name":"Department of Pediatrics University of Missouri\u2010Kansas City School of Medicine Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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