{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T19:28:03Z","timestamp":1769628483492,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off\u2010label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight\u2010based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbS\u03b2span<jats:sup>0<\/jats:sup>thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure\u2010response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open\u2010label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight\u2010based dosing schemes provide consistent drug exposure; and age\u2010based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.598","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T23:29:13Z","timestamp":1437607753000},"page":"298-306","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia"],"prefix":"10.1002","volume":"56","author":[{"given":"Jeremie H.","family":"Estepp","sequence":"first","affiliation":[{"name":"Departments of Hematology and Pathology St. Jude Children's Research Hospital Memphis TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Melloni","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Duke University Medical Center Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney D.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California\u2010San Diego La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Wiczling","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutics and Pharmacodynamics Medical University of Gda\u0144sk Gda\u0144sk Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas Southwestern Medical Center Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Duke University Medical Center Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy S.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation Columbia University Medical Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Liem","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Stem Cell Transplant, Ann &amp; Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda M.","family":"Brandow","sequence":"additional","affiliation":[{"name":"Section of Pediatric Hematology\/Oncology Medical College of Wisconsin, and Children's Research Institute of the Children's Hospital of Wisconsin Milwaukee WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley E.","family":"Crary","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\u2013Oncology University of Arkansas for Medical Sciences\/Arkansas Children's Hospital Little Rock AR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology University of Alabama at Birmingham School of Medicine Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurine H.","family":"Morris","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"The Emmes Corporation Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uttam","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Children's Mercy Hospitals and Clinics Kansas City MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Jusko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences University at Buffalo Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Neville","sequence":"additional","affiliation":[{"name":"Section of Pharmacology and Toxicology University of Arkansas for Medical Sciences and Arkansas Children's Hospital Little Rock AR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Best Pharmaceuticals for Children Act\u2014Pediatric Trials Network Administrative Core Committee*","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/ajh.21570","article-title":"The number of people with sickle\u2010cell disease in the United States: national and state estimates","volume":"85","author":"Brousseau DC","year":"2010","journal-title":"Am J Hematol"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4973"},{"issue":"5","key":"e_1_2_10_5_1","first-page":"1550","article-title":"Safety of hydroxyurea in children with sickle cell anemia: results of the HUG\u2010KIDS study, a phase I\/II trial","volume":"94","author":"Kinney TR","year":"1999","journal-title":"Blood"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12323"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21738"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.119590"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60355-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2475"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.10517"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08698.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23365"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-459-3_26"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000145"},{"key":"e_1_2_10_16_1","unstructured":"Food and Drug Administration.Statistical Approaches to Establishing Bioequivalence.2001.http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/ucm070244.pdf. 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