Effects of valproate on mitochondrial function in epileptic patients.

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Reye-like syndrome and fatal hepatic damage were recently reported in epileptic patients treated with valproate (VPA). VPA (dipropylacetate) is an organic acid, and we postulated that VPA might affect mitochondrial function in the patients taking VPA. Therefore, we studied blood levels of ammonia, carnitine, lactate, pyruvate, amino acids, 3-hydroxybutyric acid and free fatty acids in epileptic patients on VPA, whose mean age was 9.7 years (range 2 to 17 years).<BR>The subjects were divided into 3 groups; 9 patients taking VPA alone (group A), 11 patients on VPA and other antiepileptic drugs (group B) and 18 patients on antiepileptic drugs other than VPA (controls). In spite of the low therapeutic doses of VPA in group A (16.2±3.8 mg/kg/day) and in group B (19.7±6.5mg/kg/day), the levels of lactate, pyruvate and alanine were significantly elevated in both groups A and B. Additionally, a decrease in carnitine concentration and an increase in ammonia concentration were also significant in group B. These results suggested that VPA had possible adverse effects on mitochondrial function, especially in cases of polypharmacy.
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