The occurrence of C6–C10-dicarboxylic acids in urine from patients and rats treated with dipropylacetate

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Abstract

Urine from patients treated with the antiepileptic drug dipropylacetate (Valproic acid, Deprakine) has been examined for dicarboxylic acids of chain length C6–C10, i.e., adipic, suberic, and sebacic acids. The amounts of dicarboxylic acid excreted were significantly elevated in six out of eight patients and were not correlated to the dose of dipropylacetate.

Rats were found to excrete substantial amounts of all these dicarboxylic acids on the first day of dipropylacetate medication and when the rats were starved in advance the excretions were even higher. These results indicate that the metabolism of fatty acids may be inhibited by dipropylacetate.

When rats were treated with dipropylacetate for a longer period of time, the levels of excretion of dicarboxylic acid were normalized except for a minor elevation in the amount of adipic acid excreted. Starvation, however, resulted in the excretion of considerably elevated quantities of adipic acid, moderately elevated quantities of suberic acid, and almost normal amounts of sebacic acid in the urine of rats treated with dipropylacetate for several days. This pattern of dicarboxylic aciduria is typically seen in patients with ketosis. None of the rats, however, became ketotic. The possibility of an induction of the ω-oxidation by dipropylacetate is discussed.

It is concluded that dipropylacetate interferes with the endogenous fatty acid oxidation and that the dicarboxylic aciduria seen in patients treated with dipropylacetate reflects the activity of their fat metabolism.

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