{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:38:09Z","timestamp":1765294689663},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T00:00:00Z","timestamp":1415232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the safety, tolerability, and pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of pregabalin as adjunctive therapy in children with refractory partial seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a phase 1, randomized, placebo\u2010controlled, parallel\u2010group, escalating\u2010dose, multiple\u2010dose study comprising a 7\u2010day, double\u2010blind treatment period and a single\u2010blind, single dose of pregabalin administered to all children on day 8. Children in four age cohorts (1\u201323\u00a0months, 2\u20136, 7\u201311, and 12\u201316\u00a0years) received one of four doses of pregabalin (2.5, 5, 10, or 15\u00a0mg\/kg\/day) or placebo. Safety and tolerability were assessed throughout the study. Steady\u2010state and single\u2010dose <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> parameters on day 8 were analyzed using standard noncompartmental procedures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010five children received at least one dose of treatment. Four pregabalin\u2010treated children discontinued treatment, three of whom received 15\u00a0mg\/kg\/day. Two children experienced serious adverse events, one of whom received pregabalin 15\u00a0mg\/kg\/day. During double\u2010blind treatment, the most common adverse events reported in the pregabalin\u2010treated population were somnolence (27.1%) and dizziness (12.5%). Steady\u2010state pregabalin peak and total exposure in each age cohort appeared to increase linearly with dose. Apparent oral clearance (<jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>) was directly related to creatinine clearance, consistent with adults. <jats:styled-content style=\"fixed-case\">CL<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content> normalized for body weight was 43% higher in patients weighing &lt;30\u00a0kg. Steady\u2010state and single\u2010dose <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> were consistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Pregabalin at doses up to 10\u00a0mg\/kg\/day in children aged 1\u00a0month to 16\u00a0years, and at doses up to 15\u00a0mg\/kg\/day in those aged &lt;6\u00a0years, demonstrated acceptable safety and tolerability. For children weighing &lt;30\u00a0kg, a dose increase of 40% (mg\/kg dosing) is required to achieve comparable exposure with adults or children weighing \u226530\u00a0kg. These data will inform dose selection in phase 3 trials of the efficacy and safety of adjunctive pregabalin in children with refractory partial seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12830","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T18:46:08Z","timestamp":1415299568000},"page":"1934-1943","source":"Crossref","is-referenced-by-count":25,"title":["Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: A <scp>p<\/scp>hase 1, randomized controlled study"],"prefix":"10.1111","volume":"55","author":[{"given":"Donald","family":"Mann","sequence":"first","affiliation":[{"name":"Pfizer Inc Groton Connecticut U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton Connecticut U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marci 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