P-glycoprotein-mediated efflux of antiepileptic drugs: preliminary studies in mdr1a knockout mice.
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Sills GJ, Kwan P, Butler E, de Lange EC, van den Berg DJ, Brodie MJ
P-glycoprotein-mediated efflux of antiepileptic drugs: preliminary studies in mdr1a knockout mice.
Epilepsy Behav. 2002 Oct;3(5):427-432. doi: 10.1016/s1525-5050(02)00511-5.
- PubMed ID
- 12609264 [ View in PubMed]
- Abstract
Evidence suggests that the efflux transporter P-glycoprotein (P-gp) may play a facilitatory role in refractory epilepsy by limiting the brain access of antiepileptic drugs (AEDs). We have conducted a preliminary pharmacokinetic study of seven commonly used AEDs in mdr1a knockout mice, devoid of P-gp at the blood-brain barrier. A parallel group of matched wild-type mice served as controls. AEDs were administered by subcutaneous injection and serum and brain drug concentrations determined at 30, 60, and 240min post-dosing. The brain-serum concentration ratio for topiramate was higher in mdr1a(-/-) mice than in wild-type controls at all time points investigated. No consistent effects were observed with any other AED investigated. These findings suggest that topiramate may be a substrate for P-gp-mediated transport. Further studies employing a range of model systems are required to substantiate this observation and to address the potential role of drug transporters in refractory epilepsy.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Topiramate P-glycoprotein 1 Protein Humans UnknownSubstrateDetails