{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:09:44Z","timestamp":1789632584539,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"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":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Purpose:\u2002<\/jats:bold> To evaluate the pharmacokinetics and tolerability of once\u2010daily eslicarbazepine acetate (ESL) and twice\u2010daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Single\u2010center, open\u2010label, randomized, parallel\u2010group study in healthy volunteers. Volunteers in ESL group (n\u2003=\u20037) received 600\u2003mg on days 1\u20133 and 1,200\u2003mg on days 4\u20139, once daily. Volunteers in the OXC group (n\u2003=\u20037) received 300\u2003mg on days 1\u20133 and 600\u2003mg on days 4\u20139, twice daily. Plasma and CSF sampling was performed following the last dose.<\/jats:p><jats:p><jats:bold>Key Findings:\u2002<\/jats:bold> Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R\u2010licarbazepine and oxcarbazepine was approximately four\u2010fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak\u2010to\u2010trough (ratio) in the CSF for both eslicarbazepine (ESL\u2003=\u20031.5; OXC\u2003=\u20031.2) and R\u2010licarbazepine (ESL\u2003=\u20031.2; OXC\u2003=\u20031.2). In contrast, oxcarbazepine showed larger differences between peak and trough (ESL\u2003=\u20033.1; OXC =\u20036.4). A total of 84 and 24 treatment\u2010emergent adverse events (TEAEs) were reported with OXC and ESL, respectively.<\/jats:p><jats:p><jats:bold>Significance:\u2002<\/jats:bold> In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R\u2010licarbazepine, and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The smaller peak\u2010to\u2010trough fluctuation of eslicarbazepine in CSF (a measure of sustained delivery to the brain) than in plasma supports once\u2010daily dosing of ESL.<\/jats:p>","DOI":"10.1111\/j.1528-1167.2012.03595.x","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T21:41:08Z","timestamp":1342820468000},"page":"108-116","source":"Crossref","is-referenced-by-count":65,"title":["Steady\u2010state plasma and cerebrospinal fluid pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine in healthy volunteers"],"prefix":"10.1111","volume":"54","author":[{"given":"Teresa","family":"Nunes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 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