1127 SODIUM BENZOATE IN THE TREATMENT OF HYPERAMMONEMIA IN NEWBORNS

Abstract

Benzoate is effective in increasing the excretion of urinary nitrogen in patients with hyperammonemia. In jaundiced newborns, however, the potential exists for benzoate, if present at high serum concentrations, to displace bilirubin from albumin binding sites and thereby increase the risk of bilirubin toxicity. This risk was evaluated by studying the disposition of benzoate in 3 non-jaundiced newborns with severe hyperammonemia. The infants received sodium benzoate (125mg/kg i.v. q6h). Benzoate was efficiently converted to hippurate (metabolic clearance was 1.89-2.37 ml/min), whereas the urinary elimination of unchanged benzoate was minimal (clearance 0.04-0.10 ml/min). Hippurate was eliminated primarily by renal excretion. Quantitation of benzoate and hippurate in the urine and peritoneal dialysis fluid at steady state accounted for 70-120% of the administered benzoate dose. Steady state serum concentrations of benzoate ranged from 231-517 mg/L, however, the onset of renal failure in one patient led to benzoate levels exceeding 1000 mg/L despite the absence of glycine depletion. These serum concentrations, based on the known affinity constants of benzoate and bilirubin for albumin would increase the unbound fraction of bilirubin by 2 to 12 fold. Further use of this drug in newborns should be carried out with monitoring of benzoate and hippurate concentrations so that potentially toxic serum concentrations can be avoided and safe effective dosage regimens for this age group can be devised.