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Article
December 1989

On Combination Therapy With Benzoate and Piridoxilate

Author Affiliations

Department of Biochemistry and Biophysics University of Rhode Island Kingston, RI 02881

Am J Dis Child. 1989;143(12):1392. doi:10.1001/archpedi.1989.02150240014006
Abstract

Sir.—It has been amply demonstrated that administration of sodium benzoate moderates hyperammonemia in children born with genetic defects in the urea cycle,1 but the efficacy of benzoate therapy has been questioned on the basis of the limited ability of the body to generate the glycine needed to dispose of waste nitrogen as hippurate.2 Accordingly, it was recommended that piridoxilate be administered with benzoate to improve the effectiveness of benzoate therapy. Piridoxilate is a European cardiac drug found to stimulate the conversion of benzoate to hippurate in suspensions of hepatocytes, presumably because piridoxilate metabolism gives rise to glyoxylate and, by transamination, glycine.2

Piridoxilate is unavailable in the United States, so we tested the interaction of the active metabolite, glyoxylate, and benzoate. We found glyoxylate to potentiate benzoate toxicity in vivo and both drugs to inhibit pyruvate carboxylase in vitro, by apparently different mechanisms.3,4 The combination inhibited

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