Kubota K, Ishizaki T
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Eur J Clin Pharmacol. 1991;41(4):363-8. doi: 10.1007/BF00314969.
Plasma concentration-time data for benzoic and hippuric acids and urinary excretion-time data for hippuric acid were analyzed simultaneously after oral doses of 40, 80 or 160 mg/kg sodium benzoate administered at least one week apart to 6 healthy subjects. The mean AUCs of benzoic acid after the doses of 80 and 160 mg/kg of sodium benzoate were 3.7- and 12.0-times greater, respectively, than after 40 mg/kg. However, the mean AUC of hippuric acid was roughly proportional to the benzoate doses. The observed data were explained by a one-compartment model with first-order rate absorption and Michaelis-Menten elimination of benzoic acid, together with a one-compartment model with first-order elimination for hippuric acid. Although the maximum rate of biotransformation of benzoic acid to hippuric acid varied between 17.2 and 28.8 mg.kg-1.h-1 among the six individuals, the mean value (23.0 mg.kg-1.h-1) was fairly close to that provided by daily maximum dose (0.5 g.kg-1.day-1) recommended in the treatment of hyperammonaemia in patients with inborn errors of ureagenesis. The individual maximum rate of metabolism can be estimated from the urinary excretion rate of hippuric acid 1.5 to 3 h after the single oral dose of 80 to 160 mg.kg-1 sodium benzoate. The justification of this concept requires further studies in patients with inborn errors of urea synthesis.
对6名健康受试者口服40、80或160mg/kg苯甲酸钠（给药间隔至少1周）后，同时分析苯甲酸和马尿酸的血浆浓度-时间数据以及马尿酸的尿排泄-时间数据。80mg/kg和160mg/kg苯甲酸钠剂量后苯甲酸的平均AUC分别比40mg/kg剂量后高3.7倍和12.0倍。然而，马尿酸的平均AUC与苯甲酸盐剂量大致成正比。观察到的数据用一个具有一级吸收速率和米氏消除的苯甲酸单室模型，以及一个具有一级消除的马尿酸单室模型来解释。尽管6名个体中苯甲酸转化为马尿酸的最大速率在17.2至28.8mg·kg⁻¹·h⁻¹之间变化，但平均值（23.0mg·kg⁻¹·h⁻¹）与尿素生成先天性缺陷患者高氨血症治疗中推荐的每日最大剂量（0.5g·kg⁻¹·天⁻¹）相当接近。单次口服80至160mg·kg⁻¹苯甲酸钠后1.5至3小时，可根据马尿酸的尿排泄速率估算个体最大代谢速率。这一概念的合理性需要在尿素合成先天性缺陷患者中进行进一步研究。
