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• W2156826164 abstract "para-aminosalicylic acid (PAS; 4-amino-2-hydroxybenzoic acid), an antituberculosis drug in use since the 1950s, has recently been suggested to be an effective agent for treatment of manganese-induced parkinsonian disorders. However, the neuropharmacokinetics of PAS and its metabolite N-acetyl-para-aminosalicylic acid (AcPAS; N-acetyl-4-amino-2-hydroxybenzoic acid) are unknown. This study was designed to investigate the pharmacokinetics of PAS and its distribution in brain to help better design the dosing regimen for clinical trials. Male Sprague-Dawley rats received single femoral artery injections of PAS (200 mg/kg). Plasma, cerebrospinal fluid, and brain tissues were collected, and PAS and AcPAS concentrations were quantified by high-performance liquid chromatography. After administration, the concentrations of PAS declined rapidly in plasma with an elimination t(½) of 34 min; the metabolite AcPAS was detected in plasma and eliminated with a t(½) of 147 min. PAS and AcPAS were detected in brain tissues; AcPAS had a much higher tissue concentration and a longer t(½) than the parent PAS in most tissues examined. Although both were present in blood or tissues as free, unbound molecules, AcPAS appeared to have a higher tissue affinity than PAS. Taken together, our results suggest that a dosing regimen with continuous intravenous infusion of PAS is necessary to achieve therapeutic levels in targeted brain regions. Furthermore, PAS and AcPAS seem to be effective in reducing manganese levels in brain." @default.
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• W2156826164 date "2011-07-18" @default.
• W2156826164 modified "2023-09-26" @default.
• W2156826164 title "Brain Regional Pharmacokinetics of<i>p</i>-Aminosalicylic Acid and Its N-Acetylated Metabolite: Effectiveness in Chelating Brain Manganese" @default.
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• W2156826164 doi "https://doi.org/10.1124/dmd.111.040915" @default.
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