{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:51:55Z","timestamp":1790009515766,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>\n                    This study investigated the impact of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>\n                      1B1\n                    <\/jats:italic>\n                    genotype on pravastatin systemic exposure in children and adolescents with hypercholesterolemia. Participants (8\u201320\u00a0years) with at least one allelic variant of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>\n                      1B1\n                    <\/jats:italic>\n                    c.521T&gt;C (521\n                    <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>\n                    ,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a015; 521\n                    <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\n                    ,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a02) and wild\u2010type controls (521\n                    <jats:styled-content style=\"fixed-case\">TT<\/jats:styled-content>\n                    ,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a015) completed a single oral dose pharmacokinetic study. Interindividual variability of pravastatin acid (\n                    <jats:styled-content style=\"fixed-case\">PVA<\/jats:styled-content>\n                    ) exposure within\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>\n                      1B1\n                    <\/jats:italic>\n                    genotype groups exceeded the approximately twofold difference in mean\n                    <jats:styled-content style=\"fixed-case\">PVA<\/jats:styled-content>\n                    exposure observed between\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>\n                      1B1\n                    <\/jats:italic>\n                    genotype groups (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&gt;\u00a00.05,\n                    <jats:italic>q<\/jats:italic>\n                    \u00a0&gt;\u00a00.10). The 3\u2032\u03b1\u2010iso\u2010pravastatin acid and lactone isomer formation in the acidic environment of the stomach prior to absorption also was variable and affected\n                    <jats:styled-content style=\"fixed-case\">PVA<\/jats:styled-content>\n                    exposure in all genotype groups. The\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SLCO<\/jats:styled-content>\n                      1B1\n                    <\/jats:italic>\n                    c.521 gene variant contributing to variability in systemic exposure to\n                    <jats:styled-content style=\"fixed-case\">PVA<\/jats:styled-content>\n                    in our pediatric cohort was comparable to previous studies in adults. However, other demographic and physicochemical factors seem to also contribute to interindividual variability in the dose\u2013exposure relationship.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1330","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T17:51:03Z","timestamp":1544809863000},"page":"1501-1512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia"],"prefix":"10.1111","volume":"105","author":[{"given":"Jonathan B.","family":"Wagner","sequence":"first","affiliation":[{"name":"Ward Family Heart Center Children's Mercy Kansas City Missouri USA"},{"name":"Division of Clinical Pharmacology, Medical Toxicology and Therapeutic Innovation Children's 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, Medical Toxicology and Therapeutic Innovation Children's 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, Medical Toxicology and Therapeutic Innovation Children's 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, Medical Toxicology and Therapeutic Innovation Children's 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's 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's Mercy Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Kauffman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Medical Toxicology and Therapeutic Innovation Children's 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":"Leon","family":"Van Haandel","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Medical Toxicology and Therapeutic Innovation Children's 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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