P-glycoprotein-mediated efflux of antiepileptic drugs: preliminary studies in mdr1a knockout mice

Sills, G. J., Kwan, P., Butler, E., de Lange, E. C.M., van den Berg, D.-J. and Brodie, M. J. (2002) P-glycoprotein-mediated efflux of antiepileptic drugs: preliminary studies in mdr1a knockout mice. Epilepsy and Behavior, 3(5), pp. 427-432. (doi:10.1016/S1525-5050(02)00511-5) (PMID:12609264)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin and Butler, Mrs Elaine and Sills, Dr Graeme
Authors: Sills, G. J., Kwan, P., Butler, E., de Lange, E. C.M., van den Berg, D.-J., and Brodie, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Epilepsy and Behavior
Publisher:Elsevier
ISSN:1525-5050
ISSN (Online):1525-5069

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