RT Journal
A1 CYR DM, TREMBLAY GC
T1 ON combination therapy with benzoate and piridoxilate
JF American Journal of Diseases of Children
JO American Journal of Diseases of Children
YR 1989
FD December 1
VO 143
IS 12
SP 1392
OP 1392
DO 10.1001/archpedi.1989.02150240014006
UL http://dx.doi.org/10.1001/archpedi.1989.02150240014006
AB 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.2Piridoxilate 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