Limited P-glycoprotein mediated efflux for anti-epileptic drugs.

A variety of anti-epileptic drugs (AEDs) were tested for their ability to be transported by P-glycoprotein (P-gp) through Caco-2 monolayers using bi-directional (apical (Ap) to basolateral (Bas), and Bas to Ap) studies. Transport rates were equivalent in both directions for vigabatrin, gabapentin, p...

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Main Authors: Crowe, Andrew, Teoh, Y.
Format: Journal Article
Published: informa UK Ltd 2006
Online Access:http://hdl.handle.net/20.500.11937/8478
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author Crowe, Andrew
Teoh, Y.
author_facet Crowe, Andrew
Teoh, Y.
author_sort Crowe, Andrew
building Curtin Institutional Repository
collection Online Access
description A variety of anti-epileptic drugs (AEDs) were tested for their ability to be transported by P-glycoprotein (P-gp) through Caco-2 monolayers using bi-directional (apical (Ap) to basolateral (Bas), and Bas to Ap) studies. Transport rates were equivalent in both directions for vigabatrin, gabapentin, phenobarbitone, lamotrigine and carbamazepine, being 0.7 × 10− 6, 0.1 × 10− 6, 34 × 10− 6, 36 × 10− 6 and 55 × 10− 6 cm/s, respectively. Phenytoin displayed a 20% increase in Ap to Bas transport, while topiramate and ethosuximide each had greater transport in the uptake direction, with both drugs showing no efflux. None of the transport rates for these drugs were affected by P-gp inhibitors. However, the efflux rate for acetazolamide was 3-fold higher than its uptake and this was significantly reduced by P-gp inhibitors. Thus, only one anti-epileptic, acetazolamide, was shown to be weak P-gp substrate, suggesting that P-gp efflux may not be a factor in relation to the development of resistance of epilepsy therapy.
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spelling curtin-20.500.11937-84782017-09-13T15:54:28Z Limited P-glycoprotein mediated efflux for anti-epileptic drugs. Crowe, Andrew Teoh, Y. A variety of anti-epileptic drugs (AEDs) were tested for their ability to be transported by P-glycoprotein (P-gp) through Caco-2 monolayers using bi-directional (apical (Ap) to basolateral (Bas), and Bas to Ap) studies. Transport rates were equivalent in both directions for vigabatrin, gabapentin, phenobarbitone, lamotrigine and carbamazepine, being 0.7 × 10− 6, 0.1 × 10− 6, 34 × 10− 6, 36 × 10− 6 and 55 × 10− 6 cm/s, respectively. Phenytoin displayed a 20% increase in Ap to Bas transport, while topiramate and ethosuximide each had greater transport in the uptake direction, with both drugs showing no efflux. None of the transport rates for these drugs were affected by P-gp inhibitors. However, the efflux rate for acetazolamide was 3-fold higher than its uptake and this was significantly reduced by P-gp inhibitors. Thus, only one anti-epileptic, acetazolamide, was shown to be weak P-gp substrate, suggesting that P-gp efflux may not be a factor in relation to the development of resistance of epilepsy therapy. 2006 Journal Article http://hdl.handle.net/20.500.11937/8478 10.1080/10611860600720814 informa UK Ltd restricted
spellingShingle Crowe, Andrew
Teoh, Y.
Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title_full Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title_fullStr Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title_full_unstemmed Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title_short Limited P-glycoprotein mediated efflux for anti-epileptic drugs.
title_sort limited p-glycoprotein mediated efflux for anti-epileptic drugs.
url http://hdl.handle.net/20.500.11937/8478