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The uptake of valproic acid (VPA) from blood into several brain regions was investigated using the "in situ" brain perfusion technique in the rat. The uptake kinetics of VPA exhibited partial saturability and trans-stimulation, which indicate the simultaneous presence of carrier-mediated transport and diffusion. The apparent Michaelis constant for the(More)
The steady-state brain-to-free plasma concentration ratio of valproic acid (VPA) is well below unity, which suggests that it is efficiently removed from the central nervous system (CNS) by specialized transport processes. The purpose of this study was to determine whether probenecid (PBD)-sensitive anion transporters at the choroidal epithelium and brain(More)
The concentrations of valproate (VPA) and six of its pharmacologically active, unsaturated metabolites (E-delta 2-VPA, Z-delta 3-VPA, E-delta 3-VPA, E,E-delta 2,3'-VPA, delta 4-VPA, and E-delta 2,4-VPA) were measured in serum and cortical brain samples from 24 patients undergoing epilepsy surgery. Collectively, the six metabolites were present at(More)
Previous experiments suggest the primary route of valproic acid (VPA) removal from the rabbit central nervous system (CNS) is by probenecid-sensitive transporters at the blood-brain barrier but not at the choroid plexus. The purpose of this study was to determine if other transport mechanisms at the choroid plexus played a significant role in the removal of(More)
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(More)
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