Valproate, Carnitine Metabolism, and Biochemical Indicators of Liver Function

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Abstract
The effects of valproate (VPA) on carnitine and lipid metabolism and on liver function were assessed in 213 age- and sex-matched outpatients from five centers, with the following distribution: VPA monotherapy, 54; VPA polytherapy, 55; other monotherapies, 51; and untreated, 53. Mean total and free carnitine levels were significantly lower in patients with polytherapy; acylcarnitine was significantly higher for VPA monotherapy and the ratio of acyl-to-free carnitine was significantly higher in all patients receiving VPA. Ammonia, uric acid, and bilirubin were the only tests selectively impaired with VPA. A significant correlation was found between serum ammonia and VPA dosage. Glucose, .beta.-lipoproteins, tryglicerides, acetacetate, and .beta.-hydroxybutyrate were unchanged in the four groups. Sex and age appeared to interact with total and free carnitine values. Adverse drug reactions were apparently unrelated to carnitine metabolism impairment. Only a few patients had abnormal carnitine values. Our data support the assumption that carnitine deficiency and abnormal liver function due to VPA are mostly subclinical events.