{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:02:01Z","timestamp":1787724121291,"version":"build-2784847793"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T00:00:00Z","timestamp":1359417600000},"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":[[2013,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To determine whether the antiepileptic drug lacosamide affects the pharmacokinetics or pharmacodynamics of a combined oral contraceptive (<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>; ethinylestradiol 0.03\u00a0mg plus levonorgestrel 0.15\u00a0mg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an open\u2010label trial in healthy female volunteers. Eligible women entered cycle 1 of the trial on the first day of menstruation. Cycle 1 was a medication\u2010free, run\u2010in phase of approximately 28\u00a0days to confirm that normal ovulation occurred. Volunteers with confirmed ovulation entered the subsequent cycle and started taking<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>s. After establishing ovulation suppression (defined as progesterone serum concentration &lt;5.1\u00a0n<jats:sc>m<\/jats:sc>on day 21 of the menstrual cycle) in volunteers taking the<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>s in cycle 2, lacosamide 400\u00a0mg\/day was administered concomitantly in the subsequent cycle (cycle 3). The pharmacokinetic parameters of area under the concentration\u2010time curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>), maximum steady\u2010state plasma drug concentration (C<jats:sub>max<\/jats:sub>), and time to maximum concentration (t<jats:sub>max<\/jats:sub>) were measured for the<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>components and lacosamide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>A total of 37 volunteers completed cycle 1, and 32 completed cycle 2. In each of the 31 volunteers who completed the trial (through cycle 3), pharmacodynamic assessment showed progesterone serum concentration was &lt;5.1\u00a0n<jats:sc>m<\/jats:sc>on day 21 of cycle 2, when the OC was administered alone, and on day 21 of cycle 3, when lacosamide was administered concomitantly. The AUC of ethinylestradiol alone versus together with lacosamide was 1,067\u00a0\u00b1\u00a0404 versus 1,173\u00a0\u00b1\u00a0330\u00a0pg\u00a0h\/ml. Corresponding values of C<jats:sub>max<\/jats:sub>were 116.9\u00a0\u00b1\u00a048.8 versus 135.7\u00a0\u00b1\u00a028.6\u00a0pg\/ml. For levonorgestrel, the AUC alone was 74.2\u00a0\u00b1\u00a021.4 versus 80.9\u00a0\u00b1\u00a018.5\u00a0ng\u00a0h\/ml with lacosamide. Corresponding values of C<jats:sub>max<\/jats:sub>were 6.7\u00a0\u00b1\u00a01.9 versus 7.4\u00a0\u00b1\u00a01.5\u00a0ng\/ml. The AUC and C<jats:sub>max<\/jats:sub>point estimates and almost all 90% confidence intervals (except for C<jats:sub>max<\/jats:sub>of ethinylestradiol) for ethinylestradiol and levonorgestrel (with and without lacosamide) were within the conventional bioequivalence range, and no relevant changes in t<jats:sub>max<\/jats:sub>were observed for ethinylestradiol (1.5\u00a0\u00b1\u00a00.6\u00a0h alone vs. 1.4\u00a0\u00b1\u00a00.7\u00a0h with lacosamide) or for levonorgestrel (1.5\u00a0\u00b1\u00a01.0\u00a0h alone vs. 1.1\u00a0\u00b1\u00a00.6\u00a0h with lacosamide). Lacosamide pharmacokinetics were consistent with those observed in previous studies of lacosamide alone, with values for AUC of 113.5\u00a0\u00b1\u00a020.7\u00a0\u03bcg\u00a0h\/ml, C<jats:sub>max<\/jats:sub>of 13.8\u00a0\u00b1\u00a02.2\u00a0\u03bcg\/ml, and t<jats:sub>max<\/jats:sub>of 1.1\u00a0\u00b1\u00a00.4\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Lacosamide and an<jats:styled-content style=\"fixed-case\">OC<\/jats:styled-content>containing ethinylestradiol and levonorgestrel have low potential for drug\u2013drug interaction; therefore, coadministration of the two drugs is unlikely to result in contraceptive failure or loss of seizure control.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12085","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T15:58:43Z","timestamp":1359475123000},"page":"530-536","source":"Crossref","is-referenced-by-count":55,"title":["Pharmacodynamic and pharmacokinetic evaluation of 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