Effect of para-aminohippurate on the efflux of valproic acid from the central nervous system of the rabbit

Epilepsy Research
K D AdkisonD D Shen

Abstract

Recently we investigated the mechanisms mediating the transport of valproic acid (VPA) between blood and brain. In one study efflux of valproic acid (VPA) from rabbit brain was inhibited by probenecid. Efflux of VPA decreased when probenecid was given intravenously but not when probenecid was given by ventriculocisternal (VC) perfusion indicating that the major site of probenecid-sensitive transport was at the brain capillary endothelium and not at the choroid plexus. In another study VPA transport into rat brain was inhibited by para-aminohippurate (PAH). The purpose of the present study were to determine (a) if the efflux of VPA from rabbit brain was also inhibited by PAH, and (b) whether efflux of VPA could occur at the choroid plexus via an PAH-selective transport system. Six control rabbits received VPA by intravenous infusion and tracer concentrations of [3H]VPA and [14C]PAH by VC perfusion. Rabbits in the PAH group (n = 6) received identical treatment with VPA, tracer concentrations of [3H]VPA and [14C]PAH and, in addition, received 20 mM PAH by VC perfusion. PAH had no effect on the VC extraction ratio of [3H]VPA or the steady-state brain concentration of intravenously administered VPA. It is concluded that the efflux o...Continue Reading

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Citations

May 4, 2001·European Journal of Pharmacology·F UshigomeY Sawada
Jan 1, 1997·Life Sciences·J P Bolaños, J M Medina
Jan 22, 2003·Advanced Drug Delivery Reviews·Haiying SunWilliam F Elmquist
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Aug 11, 2006·Alcoholism, Clinical and Experimental Research·Scott E ParnellWei-Jung A Chen

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