Green T P, Marchessault R P, Freese D K
J Pediatr. 1983 May;102(5):785-90. doi: 10.1016/s0022-3476(83)80259-5.
Sodium benzoate lowers serum ammonia concentrations by the activation of a non-urea cycle pathway of ammonia removal. The disposition of sodium benzoate was monitored in four hyperammonemic newborn infants, using a simple and newly developed assay for benzoate and hippurate, to assess (1) the metabolic capability of patients of this age to utilize this pathway for nitrogen removal, (2) the potential risks of benzoate toxicity at clinically achieved serum benzoate concentrations, and (3) the value of routine monitoring of serum benzoate concentrations in this patient population. In three of the four infants, more than half of the administered benzoate was converted to hippurate. Hippurate was effectively cleared by the neonatal kidney, although removal of unconjugated benzoate by peritoneal dialysis or urinary excretion was slow compared with the metabolic conversion to hippurate. There was a considerable interpatient variability in benzoate metabolism; consequently, an eight-fold range in serum benzoate concentrations (2.14 to 16.0 mM/L) was found after patients had received benzoate for longer than 24 hours. These serum benzoate concentrations were calculated to be capable of producing substantial (four to 25 times) increases in free bilirubin concentrations in jaundiced infants. Although sodium benzoate offers considerable promise for the treatment of hyperammonemia, toxicity appears likely in some infants receiving this drug in currently recommended doses. Monitoring of serum concentrations appears to be warranted. Dosage reduction in jaundiced infants and in those with demonstrated insufficiency of benzoate metabolism is recommended.
苯甲酸钠通过激活一条非尿素循环的氨清除途径来降低血清氨浓度。采用一种简单且新开发的苯甲酸盐和马尿酸盐检测方法，对4例高氨血症新生儿的苯甲酸钠处置情况进行监测，以评估：（1）该年龄段患者利用此途径进行氮清除的代谢能力；（2）临床达到的血清苯甲酸盐浓度下苯甲酸盐毒性的潜在风险；（3）对该患者群体进行血清苯甲酸盐浓度常规监测的价值。在4例婴儿中的3例中，超过一半给予的苯甲酸盐转化为了马尿酸盐。马尿酸盐可被新生儿肾脏有效清除，尽管与代谢转化为马尿酸盐相比，通过腹膜透析或尿液排泄清除未结合苯甲酸盐的速度较慢。苯甲酸盐代谢存在相当大的个体间差异；因此，在患者接受苯甲酸盐超过24小时后，血清苯甲酸盐浓度出现了8倍的范围（2.14至16.0 mM/L）。据计算，这些血清苯甲酸盐浓度能够使黄疸婴儿的游离胆红素浓度大幅升高（4至25倍）。尽管苯甲酸钠在治疗高氨血症方面前景可观，但目前按推荐剂量接受该药物治疗的一些婴儿可能会出现毒性反应。似乎有必要监测血清浓度。建议对黄疸婴儿以及那些已证明苯甲酸盐代谢不足的婴儿减少剂量。
