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EFFECT OF Na BENZOATE ON SERUM BILIRUBIN IN THE GUNN RAT

That Na benzoate will displace bilirubin from albumin has been demonstrated in vitro; however, bilirubin-albumin kinetics may not be altered in vivo by Na benzoate because of its rapid conversion to Na hippurate. Of particular concern is whether the available injectable diazepam, which contains Na benzoate in its liquid vehicle, is safe to administer to newborns for such conditions as seizures or narcotics withdrawal. The Gunn rat was used as an experimental model for the displacement of bilirubin from albumin by serially measuring the fall in serum bilirubin following I.P. or I.M. administration of Na benzoate. Control animals were injected with saline. 26 animals were given 7 or 35mgs/kg of Na benzoate (equivalent to 2 or 10mg diazepam in a 3kg infant) as a single injection and 7 rats were given the same doses repeated 2 times at 1 hour intervals Serum bilirubin was determined at 10, 20 and 60 minutes after injection. No differences were found in mean bilirubin levels between control and treated rats. With repeated benzoate injections of 35mg/kg or a single dose of 100mg/kg some depression of serum bilirubin occurred; but only at 200mg/kg did bilirubin levels fall to the extent observed in the Gunn rat with similar doses of sulfasoxazole. These data suggest that recommended doses of diazepam for neonates do not contain sufficient Na benzoate to alter bilirubin binding capacities in vivo and thus are safe.