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Vamorolone, a dissociative steroidal anti\u2010inflammatory drug for treating Duchenne muscular dystrophy (DMD), primarily undergoes oxidation by CYP3A4 and CYP3A5 and glucuronidation by UDP\u2010glucuronosyltransferases. This work assesses the pharmacokinetics (PKs) of vamorolone and sources of interindividual variability (IIV) in 81 steroid\u2010na\u00efve boys with DMD aged 4 to &lt;7 years old considering the genetic polymorphisms of CYPS3A4 (CYP3A4*22, CYP3A4*1B), CYP3A5 (CYP3A5*3), and UGT1A1 (UGT1A1*60) utilizing population PK modeling. A one\u2010compartment model with zero\u2010order absorption (T<jats:sub>k0<\/jats:sub>, duration of absorption), linear clearance (CL\/F), and volume (V\/F) describes the plasma PK data for boys with DMD receiving a wide range of vamorolone doses (0.25\u20106 mg\/kg\/day). The typical CL\/F and V\/F values of vamorolone were 35.8 L\/h and 119 L, with modest IIV. The population T<jats:sub>k0<\/jats:sub> was 3.14 h yielding an average zero\u2010order absorption rate (k<jats:sub>0<\/jats:sub>) of 1.16 mg\/kg\/h with similar absorption kinetics across subjects at the same vamorolone dose (i.e., no IIV on T<jats:sub>k0<\/jats:sub>). The covariate analysis showed that none of the genetic covariates had any significant impact on the PKs of vamorolone in boys with DMD. Thus, the PKs of vamorolone is very consistent in these young boys with DMD.<\/jats:p>","DOI":"10.1002\/jcph.2446","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T12:43:42Z","timestamp":1714394622000},"page":"1130-1140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing Pharmacogenomic <i>loci<\/i> Associated with the Pharmacokinetics of Vamorolone in Boys with Duchenne Muscular Dystrophy"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-4940","authenticated-orcid":false,"given":"Xiaonan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo State University of New York  Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Sabbatini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Padova  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Padova  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Bello","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Padova  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Guglieri","sequence":"additional","affiliation":[{"name":"John Walton Centre for Neuromuscular Disease Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Hospital  Washington DC USA"},{"name":"ReveraGen BioPharma  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Damsker","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McCall","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utkarsh J.","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Carleton University  Ottawa Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"ReveraGen BioPharma  Rockville MD USA"},{"name":"Department of Pharmaceutical Sciences Binghamton University 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