{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:06:44Z","timestamp":1768824404310,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,16]],"date-time":"2015-05-16T00:00:00Z","timestamp":1431734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Lundbeck LLC"},{"name":"Allaysis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the safety, tolerability, and comparative pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of intravenous and oral carbamazepine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase 1, open\u2010label study, adult patients with epilepsy on a stable oral carbamazepine dosage (400\u20132,000\u00a0mg\/day) were converted to intravenous carbamazepine (administered at 70% of the oral dosage). A 28\u2010day outpatient period preceded an up to 10\u2010day inpatient period and a 30\u2010day follow\u2010up period. <jats:styled-content style=\"fixed-case\">Intravenous<\/jats:styled-content> carbamazepine was administered over 15 or 30\u00a0min every 6\u00a0h on days 1\u20137; some patients in the 15\u2010min group were eligible to receive four 2\u2010 to 5\u2010min (rapid) infusions on day 8. Patients underwent blood sampling to determine the area under the concentration\u2013time curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) for carbamazepine and metabolite carbamazepine\u201010,11\u2010epoxide following oral (day 0) and intravenous carbamazepine administration (days 1, 7, and 8). Bioequivalence was evaluated in patients with normal renal function (creatinine clearance &gt;80\u00a0<jats:styled-content style=\"fixed-case\">ml<\/jats:styled-content>\/min). Safety assessments were conducted through day 38.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ninety\u2010eight patients enrolled and 77 completed the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> component. The mean daily oral and intravenous carbamazepine dosage for 64 <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\u2010evaluable patients with normal renal function was 962.5 and 675.1\u00a0mg (70% of oral dosage), respectively. Steady\u2010state minimum concentration (C<jats:sub>min<\/jats:sub>) and overall exposure (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>0\u201324<\/jats:sub>) for <jats:styled-content style=\"fixed-case\">intravenous<\/jats:styled-content> carbamazepine infused over 30, 15, or 2\u20135\u00a0min were similar to oral carbamazepine. The 90% confidence intervals (<jats:styled-content style=\"fixed-case\">CIs<\/jats:styled-content>) for the ratios of the adjusted means for <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>0\u201324<\/jats:sub>, maximum concentration (C<jats:sub>max<\/jats:sub>), and C<jats:sub>min<\/jats:sub> were within the 80%\u2013125% bioequivalence range for 30\u2010min <jats:styled-content style=\"fixed-case\">intravenous<\/jats:styled-content> infusions versus oral administration, but exceeded the upper limit for C<jats:sub>max<\/jats:sub> for the 15\u2010min and rapid infusions. All intravenous carbamazepine infusions were well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">Intravenous<\/jats:styled-content> carbamazepine infusions (70% of oral daily dose) of 30\u2010, 15\u2010, and 2\u2010 to 5\u2010min duration, given every 6\u00a0h, maintained patients\u2019 plasma carbamazepine concentrations. <jats:styled-content style=\"fixed-case\">Intravenous<\/jats:styled-content> carbamazepine 30\u2010min infusions were bioequivalent to oral carbamazepine in patients with normal renal function; rapid infusions were well\u2010tolerated in this study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13012","type":"journal-article","created":{"date-parts":[[2015,5,16]],"date-time":"2015-05-16T08:33:17Z","timestamp":1431765197000},"page":"915-923","source":"Crossref","is-referenced-by-count":14,"title":["Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy"],"prefix":"10.1111","volume":"56","author":[{"given":"Dwain","family":"Tolbert","sequence":"first","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Cloyd","sequence":"additional","affiliation":[{"name":"Center for Orphan Drug Research College of Pharmacy University of Minnesota Minneapolis Minnesota U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Biton","sequence":"additional","affiliation":[{"name":"Arkansas Epilepsy Program Little Rock Arkansas U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ihor","family":"Bekersky","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Walzer","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wesche","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Drummond","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Lee","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield Illinois U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,16]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO Model List of Essential Medicines.2013.http:\/\/www.who.int\/medicines\/publications\/essentialmedicines\/en\/index.html. 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