{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:15:10Z","timestamp":1789676110399,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"BIAL - Portela & C\u00aa, S.A."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,8]]},"abstract":"Summary<\/jats:title>\n \n Purpose<\/jats:title>\n \n Investigate the pharmacokinetics of once\u2010daily (\n QD<\/jats:styled-content>\n ; 900\u00a0mg) and twice\u2010daily (\n BID<\/jats:styled-content>\n ; 450\u00a0mg) regimens of eslicarbazepine acetate (\n ESL<\/jats:styled-content>\n ) and\n BID<\/jats:styled-content>\n (450\u00a0mg) regimen of oxcarbazepine (\n OXC<\/jats:styled-content>\n ) at steady state in healthy volunteers.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Single\u2010center, open\u2010label, randomized, three\u2010way (n\u00a0=\u00a012) crossover studies in healthy volunteers.<\/jats:p>\n <\/jats:sec>\n \n Key Findings<\/jats:title>\n \n Mean eslicarbazepine C\n max,ss<\/jats:sub>\n (in \u03bc\n m<\/jats:sc>\n ) following\n ESL QD<\/jats:styled-content>\n (87.3) was 33.3% higher (p\u00a0<\u00a00.05) compared to\n ESL BID<\/jats:styled-content>\n (65.5) and 82.1% higher (p\u00a0<\u00a00.05) compared to\n OXC BID<\/jats:styled-content>\n (48.0). The mean area under the curve (\n AUC<\/jats:styled-content>\n )\n ss,0\u2013\u03c4<\/jats:sub>\n (in \u03bcmol\u00a0h\/L) following the last dose of an 8\u2010day repeated dosing was 1156.3, 1117.6, and 968.4 for\n ESL QD<\/jats:styled-content>\n ,\n ESL BID<\/jats:styled-content>\n , and\n OXC BID<\/jats:styled-content>\n , respectively. The ratio eslicarbazepine plasma exposure (\u03bcmol\u00a0h\/L) to\n ESL<\/jats:styled-content>\n daily\u2010dose (\u03bcmol) was 0.381 (1156.3:3037.3), 0.368 (1117.6:3037.3), and 0.271 (968.4:3567.6) for\n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n ,\n ESL<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , and\n OXC<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , respectively, which translates into a 40.6% increase in the ability of\n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n compared to\n OXC<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n to deliver into the plasma their major active entity eslicarbazepine. The extent of plasma exposure to\n ESL<\/jats:styled-content>\n minor metabolites: (R)\u2010licarbazepine and oxcarbazepine after\n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n was 71.5% and 61.1% lower, respectively, than after\n OXC<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n . Twenty, 24 and 38 treatment emergent adverse events were reported with\n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n ,\n ESL<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , and\n OXC<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n resulted in 33.3% higher peak plasma concentration (C\n max,ss<\/jats:sub>\n ) of eslicarbazepine and similar extent of plasma exposure (\n AUC<\/jats:styled-content>\n ss,0\u2013\u03c4<\/jats:sub>\n ) when compared to\n ESL<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , which may contribute to the efficacy profile reported with once\u2010daily\n ESL<\/jats:styled-content>\n . In comparison to\n OXC<\/jats:styled-content>\n \u2010\n BID<\/jats:styled-content>\n , administration of\n ESL<\/jats:styled-content>\n \u2010\n QD<\/jats:styled-content>\n resulted in 40.6% increase in the delivery of eslicarbazepine into the plasma as well as a significantly lower systemic exposure to (R)\u2010licarbazepine and oxcarbazepine.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/epi.12242","type":"journal-article","created":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T13:25:13Z","timestamp":1371043513000},"page":"1453-1461","source":"Crossref","is-referenced-by-count":44,"title":["Pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine at steady state in healthy volunteers"],"prefix":"10.1111","volume":"54","author":[{"given":"Christian","family":"Elger","sequence":"first","affiliation":[{"name":"Department of Epileptology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meir","family":"Bialer","sequence":"additional","affiliation":[{"name":"Institute for Drug Research Faculty of Medicine School of Pharmacy Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00edlcar","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Coimbra Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Vaz\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"BIAL \u2013 Portela & C\u00aa, S.A. 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