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• W2167863485 abstract "Recent studies have suggested that overexpression of the multidrug transporter P-glycoprotein (P-gp) in the hippocampal region leads to decreased levels of antiepileptic drugs and contributes to pharmacoresistance that occurs in a subset of epileptic patients. Whether P-gp expression and function is affected in other brain regions and in organs that are involved in drug metabolism is less studied. Therefore, we investigated P-gp expression in different brain regions and liver of chronic epileptic rats, several months after electrically induced status epilepticus (SE), using Western blot analysis. P-gp function was determined by measuring phenytoin (PHT) levels in these brain regions using high-performance liquid chromatography, in the absence and presence of a P-gp-specific inhibitor, tariquidar (TQD). In addition, the pharmacokinetic profile of PHT was determined. PHT concentration was reduced by 20 to 30% in brain regions that had P-gp overexpression (temporal hippocampus and parahippocampal cortex) and not in brain regions in which P-gp expression was not changed after SE. Inhibition of P-gp by TQD significantly increased the PHT concentration, specifically in regions that showed P-gp overexpression. Despite increased P-gp expression in the liver of epileptic rats, pharmacokinetic analysis showed no significant change of PHT clearance in control versus epileptic rats. These findings show that overexpression of P-gp at the blood-brain barrier of specific limbic brain regions causes a decrease of local PHT levels in the rat brain." @default.
• W2167863485 created "2016-06-24" @default.
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• W2167863485 date "2007-03-28" @default.
• W2167863485 modified "2023-10-17" @default.
• W2167863485 title "Region-Specific Overexpression of P-glycoprotein at the Blood-Brain Barrier Affects Brain Uptake of Phenytoin in Epileptic Rats" @default.
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• W2167863485 doi "https://doi.org/10.1124/jpet.107.121178" @default.
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