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 240 min 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.
Original language | English |
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Pages (from-to) | 427-432 |
Number of pages | 6 |
Journal | Epilepsy and Behavior |
Volume | 3 |
Issue number | 5 |
DOIs | |
Publication status | Published - 1 Oct 2002 |
Externally published | Yes |
Keywords
- Antiepileptic drugs
- Multidrug resistance
- P-glycoprotein
- Pharmacokinetics
- Refractory epilepsy