PMID: 2512113Nov 1, 1989Paper

Beta-oxidation of valproate. II. Effects of fasting, glucose, and clofibrate in rats

Epilepsia
K M KochR H Levy

Abstract

The effects of glucose infusion, fasting, and clofibrate pretreatment on valproate (VPA) disposition were investigated in rats to determine the role of endogenous fatty acid beta-oxidation in the metabolic formation of 2-en-VPA. Rats undergoing each treatment received a continuous steady-state infusion of VPA and a single intravenous (i.v.) bolus of 2-en-VPA. Elimination clearance of VPA was significantly higher (median 31%, p = 0.002) with glucose infusion as compared with fasting but was unchanged by clofibrate pretreatment as compared with control. Formation clearance of 2-en-VPA was significantly higher with glucose infusion as compared with fasting (median 147%, p = 0.001) and with clofibrate pretreatment as compared with control (median 73%, p = 0.041). Fractional metabolism of VPA by this route averaged 6% in fasted and control rats and 10% in glucose-infused and clofibrate-pretreated rats. Thus, VPA elimination clearance was not greatly influenced by effects on this route in rats. Elimination clearance of 2-en-VPA was also higher with glucose infusion as compared with fasting (median 149%, p = 0.002), and with clofibrate pretreatment as compared with control (median 167%, p less than 0.001). These observations are consi...Continue Reading

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Citations

Jun 19, 1992·Pharmaceutisch Weekblad. Scientific Edition·F Pisani
May 25, 2002·Epilepsia·Angélica M Bello-RamírezAlejandro A Nava-Ocampo
Apr 16, 2002·Journal of Child Neurology·Raj D Sheth

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