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Updated: Jan 6, 2026
Isolation of Cerebral Capillaries from Fresh Human Brain Tissue
Published on: September 12, 2018
In vitro assessment of P-glycoprotein-mediated antiseizure medications efflux in a blood-brain barrier cell model
Priyanka Rani Paul1,2, Shivangi Bora1,3, Ankit Srivastava1,4
1Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India.
Objectives:
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-brain barrier (BBB), which may cause ASM efflux and limit bioavailability. Therefore, this study aimed to evaluate the potential of ASMs as P-gp substrates.
Methods:
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.
Key Findings:
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 > 1.5 in a bidirectional transport assay, which was significantly reduced in the presence of a P-gp inhibitor (P < .01).
Conclusions:
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.
