感冒灵颗粒中对乙酰氨基酚在人体的代谢特征研究

Human metabolism of acetaminophen in Ganmaoling granules

目的研究感冒灵颗粒中对乙酰氨基酚(APAP)在人体的代谢特征。方法 12名健康志愿者单次口服感冒灵颗粒后,收集尿液,采用LC-MS/MS法测定尿液中4种代谢物(葡萄糖醛酸结合物、硫酸结合物、半胱氨酸结合物和乙酰半胱氨酸结合物)的浓度,与常规剂量比较代谢产物的排泄总量及排泄比例。结果单次口服感冒灵颗粒(含APAP 200 mg)后24 h内,4种代谢物总排泄量占给药剂量的(49.1±16.74)%,毒性代谢物排泄率与总代谢物排泄率的比值为(7.7±0.08)%,与常规剂量相比,4种代谢物总排泄率降低,毒性代谢物排泄率与总代谢物排泄率的比值不变。结论感冒灵颗粒中小剂量APAP毒性代谢途径比例未发生改变,而毒性代谢物绝对量呈非线性地显著降低。提示感冒灵颗粒组方可能具有较好的安全性。

Objective To study the human metabolism of acetaminophen（APAP） in Ganmaoling granules. Methods Twelve healthy volunteers were given a single oral dose of Ganmaoling granules containing APAP 200 mg. Urine samples were collected at designated time points. Urine concentrations of the major metabolites were quantified by a selective and sensitive LC-MS/MS method. We compared the difference in the urinary excretion amount and proportion of the metabolites between the current dose and the conventional dose of acetaminophen. Results In the singledose study, the total urinary excretion rate of the 4 metabolites at 24 h was equivalent to（49.1±16.74）% of the administered dose, and the ratio of the urinary excretion rate of the toxic metabolites to the total urinary excretion rate of the metabolites was（7.7±0.08）%. Compared with the conventional dose, the total urinary excretion rate was reduced; the ratio of the toxic metabolites to the all metabolites did not change. Conclusion Small doses of APAP do not change the proportion of the toxic metabolic pathways, but the absolute amount of toxic metabolites is significantly decreased non-linearly, indicating Ganmaoling formula is safe.