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- W1569486609 abstract "VPA is associated with an idiosyncratic hepatotoxicity that is most prevalent in children under 2 years of age receiving concurrent enzyme-inducing anti-epileptic drugs. The goal of this study was to establish the limits of normal variability in VPA metabolite patterns in a population of children. Urine was collected over a steady state dosing interval in 91 pediatric patients aged 2 to 17 years receiving VPA either as monotherapy or polytherapy, and analyzed by GC-MS methods for VPA and 14 metabolites. Principal components analysis of the log-transformed metabolite data (corrected for urinary creatinine) revealed three distinct clusters of metabolites generally corresponding to microsomal biotransformation, mitochondrial beta-oxidation, and N-acetylcysteine (NAC) metabolites derived from glutathione (GSH)-conjugates of (E)-2,4-diene. If NAC conjugates are the products of reactive metabolite formation and GSH conjugation in mitochondria and free 2,4-diene-VPA is derived from a non-reactive microsomal pathway, we hypothesize that the NAC-VPA/2,4-diene ratio may reflect interindividual variability in bioactivation and detoxification capacity. A Q-Q plot of the log-transformed ratio implies a bimodal distribution that is being evaluated as a potential biomarker for VPA-toxicity in this population. Supported by grant U01 HD-044239 from NICHD" @default.
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- W1569486609 date "2008-03-01" @default.
- W1569486609 modified "2023-10-16" @default.
- W1569486609 title "Variability in valproic acid (VPA) metabolite signatures in children" @default.
- W1569486609 doi "https://doi.org/10.1096/fasebj.22.1_supplement.1131.7" @default.
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