{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:06:26Z","timestamp":1772118386138,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T00:00:00Z","timestamp":1364515200000},"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":[[2013,7]]},"abstract":"Summary<\/jats:title>Purpose<\/jats:title>Antiepileptic drugs (AED<\/jats:styled-content>s) do not effectively treat 30\u201340% of patients with epilepsy. Export of AED<\/jats:styled-content>s by P<\/jats:styled-content>\u2010glycoprotein (P<\/jats:styled-content>gp, ABCB1<\/jats:italic><\/jats:styled-content>, or MDR1<\/jats:italic><\/jats:styled-content>), which is overexpressed in the blood\u2013brain barrier in drug\u2010resistant patients, may be a mechanism for resistance to AED<\/jats:styled-content>s. For most recently approved AED<\/jats:styled-content>s, whether they are transported by P<\/jats:styled-content>gp is unknown. We investigated whether a new AED<\/jats:styled-content>, lacosamide (LCM<\/jats:styled-content>), is a substrate of human P<\/jats:styled-content>gp.<\/jats:p><\/jats:sec>Methods<\/jats:title>LLC<\/jats:styled-content>\u2010PK<\/jats:styled-content>1 and MDCKII<\/jats:styled-content> cells transfected with the human MDR<\/jats:styled-content>1<\/jats:italic> gene were used to determine the substrate status of LCM<\/jats:styled-content> in concentration equilibrium transport assays (CETAs<\/jats:styled-content>). An equal concentration of drug was initially loaded in both the apical and basal chambers, and the concentration in both chambers was measured up to 4\u00a0h. The experiments were repeated in the presence of the P<\/jats:styled-content>gp inhibitors verapamil and tariquidar. Caco\u20102 assays were used to determine the intrinsic permeability and efflux ratio of LCM<\/jats:styled-content> as well as its potential to inhibit digoxin, a P<\/jats:styled-content>gp substrate.<\/jats:p><\/jats:sec>Key Findings<\/jats:title>Lacosamide was transported by MDR1<\/jats:italic><\/jats:styled-content>\u2010transfected cells from basolateral to apical sides. The efflux of LCM<\/jats:styled-content> could be completely blocked by verapamil or tariquidar. In C<\/jats:styled-content>aco\u20102 assays, LCM<\/jats:styled-content> showed high permeability without a significant efflux ratio; it did not inhibit digoxin, a P<\/jats:styled-content>gp substrate.<\/jats:p><\/jats:sec>Significance<\/jats:title>Although LCM<\/jats:styled-content> is a substrate of P<\/jats:styled-content>gp in CETA<\/jats:styled-content>, C<\/jats:styled-content>aco\u20102 data demonstrated that passive diffusion should play a major role in the overall disposition of LCM<\/jats:styled-content>. The critical role of P<\/jats:styled-content>gp should be addressed in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12158","type":"journal-article","created":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T12:49:37Z","timestamp":1364561377000},"page":"1154-1160","source":"Crossref","is-referenced-by-count":26,"title":["Potential role for human P\u2010glycoprotein in the transport of lacosamide"],"prefix":"10.1111","volume":"54","author":[{"given":"Chunbo","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy The Chinese University of Hong Kong Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugues","family":"Chanteux","sequence":"additional","affiliation":[{"name":"UCB Pharma Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Zuo","sequence":"additional","affiliation":[{"name":"School of Pharmacy The Chinese University of Hong Kong Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Kwan","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong China"},{"name":"Departments of Medicine and Neurology The University of Melbourne Royal Melbourne Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Baum","sequence":"additional","affiliation":[{"name":"School of Pharmacy The Chinese University of Hong Kong Hong Kong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00128-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.102491"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.07.038"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-0987(00)00141-X"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200969040-00005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.12301.x"},{"key":"e_1_2_7_8_1","first-page":"64","volume-title":"Guidance for industry: drug interaction studies \u2013 study design, data analysis, implications for dosing, and labeling recommendations","author":"Food and Drug Administration","year":"2012"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135308"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.31904.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004418"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1728"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.08.032"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-009-9961-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp800122b"},{"issue":"4","key":"e_1_2_7_16_1","first-page":"2","article-title":"Lacosamide has low potential for drug\u2010drug interaction","volume":"50","author":"Thomas D","year":"2009","journal-title":"Epilepsia"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb01657.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.1.2.175"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2007.12.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.054197"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-005-5303-7"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.04.008"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03140.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.12.003"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12158","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T02:05:10Z","timestamp":1696298710000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,29]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1111\/epi.12158"],"URL":"https:\/\/doi.org\/10.1111\/epi.12158","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,29]]}}}