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)
Full text not currently available from Enlighten.
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 > School of Cardiovascular & Metabolic Health 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 |
University Staff: Request a correction | Enlighten Editors: Update this record