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- W2048490388 abstract "The effects of valproate (VPA) on free and total bilirubin concentrations in plasma were studied in guinea pigs. Steady-state hyperbilirubinemia (around 2.5-3.0 mg/100 mL) was induced by constant intravenous (i.v.) infusion of bilirubin followed by an i.v. bolus dose of sodium valproate (VPA-Na) of 50 (n = 4) or 200 (n = 5) mg/kg. Steady-state plasma total bilirubin concentration was lowered by 40% and 55% and the unbound fraction (fu) increased by 1.9- and 4.9-fold at the respective doses of 50 mg/kg and 200 mg/kg VPA-Na. Free bilirubin was not significantly changed by 50 mg/kg VPA-Na, but did show a significant transient elevation with the 200 mg/kg dose. In another experiment, guinea pigs (n = 3) were given a constant i.v. infusion of VPA-Na to maintain a steady-state plasma concentration (58 micrograms/mL), followed by an i.v. bolus dose of bilirubin (2 mg/kg). A control study (n = 3) was performed simultaneously using normal saline instead of VPA. Free bilirubin was detectable only following induction of hyperbilirubinemia in either group. A higher volume of distribution and lower elimination rate constant of bilirubin were observed in the VPA-treated than in the control animals. The displacement effect of VPA on bilirubin-plasma binding in vitro was studied by adding serial concentrations of VPA-Na to bilirubin-plasma solution. VPA displaced bilirubin from the high-affinity plasma protein binding site, with a binding constant (KD) of 5.7 x 10(-2)/microM. Similar displacement of bilirubin plasma protein binding was observed in vivo. These results suggest that VPA reduces plasma protein binding and slows the elimination rate of bilirubin. The principal mechanism for decreased plasma concentrations of total bilirubin by administration of VPA is caused by decreased plasma binding, as opposed to metabolic induction." @default.
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- W2048490388 title "Effect of Valproate on the Pharmacokinetics of Free and Total Plasma Bilirubin in Experimental Hyperbilirubinemia in Guinea Pigs" @default.
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- W2048490388 doi "https://doi.org/10.1021/js970236+" @default.
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