{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:16:09Z","timestamp":1782947769827,"version":"3.54.5"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CSIR-Institute of Genomics and Integrative Biology","award":["OLP 2301"],"award-info":[{"award-number":["OLP 2301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Drug-resistant epilepsy affects 30% of patients, where antiseizure medications (ASMs) are non-effective. A possible mechanism is the presence of the P-glycoprotein (P-gp) transporter in the blood\u2013brain barrier (BBB), which may cause ASM efflux and limit bioavailability. Therefore, this study aimed to evaluate the potential of ASMs as P-gp substrates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study was conducted using the BBB model cell line human cerebral microvascular endothelial cells (hCMEC\/D3). Ten widely used ASMs were assessed for their interaction with P-gp through in vitro assays: ATPase, competitive substrate efflux, and bidirectional transport assay, followed by quantification using HPLC or liquid chromatography-tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Valproic acid, lamotrigine, and topiramate stimulated basal ATPase activity of P-gp. In a competitive substrate efflux assay, valproic acid, lamotrigine, and topiramate increased rhodamine123 intracellular accumulation, thereby influencing its P-gp-mediated efflux. Valproic acid and lamotrigine exhibited an efflux ratio\u2009&amp;gt;\u20091.5 in a bidirectional transport assay, which was significantly reduced in the presence of a P-gp inhibitor (P\u2009&amp;lt;\u2009.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings support that valproic acid and lamotrigine are likely substrates of P-gp at the BBB. Thus, targeting the P-gp-mediated efflux may represent a promising strategy for managing drug-resistant epilepsy against these ASMs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf099","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:11:04Z","timestamp":1758888664000},"source":"Crossref","is-referenced-by-count":4,"title":["<i>In vitro<\/i>\n                    assessment of P-glycoprotein-mediated antiseizure medications efflux in a blood\u2013brain barrier cell model"],"prefix":"10.1093","volume":"78","author":[{"given":"Priyanka Rani","family":"Paul","sequence":"first","affiliation":[{"name":"Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR) , Mall Road, Delhi 110007 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivangi","family":"Bora","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR) , Mall Road, Delhi 110007 ,","place":["India"]},{"name":"Department of Biotechnology, Delhi Technological University , Shahbad Daulatpur, Main Bawana Road, Delhi 110042 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR) , Mall Road, Delhi 110007 ,","place":["India"]},{"name":"Department of Pharmacology, School of Pharmaceutical Education and Research , Jamia Hamdard, New Delhi 110062 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samiksha","family":"Kukal","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR) , Mall Road, Delhi 110007 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish Kumar","family":"Mishra","sequence":"additional","affiliation":[{"name":"Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR) , Mall Road, Delhi 110007 ,","place":["India"]},{"name":"Department of Biotechnology, Delhi Technological University , Shahbad Daulatpur, Main Bawana Road, Delhi 110042 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