叔丁基对苯二酚两种代谢物的代谢动力学

目的：研究叔丁基对苯二酚(TBHQ)在Sprague-Dawley大鼠体内的两种代谢物叔丁基对苯二酚-硫酸结合物和叔丁基对苯二酚-葡萄糖醛酸结合物的代谢动力学特征。方法：大鼠灌胃不同剂量叔丁基对苯二酚后，采用液相色谱-质谱联用法分别对两种代谢物在不同时间点血清中的浓度进行半定量分析，并运用实用药代动力学软件进行房室模型拟合及代谢动力学参数计算。结果：两种代谢物在大鼠体内的代谢动力学过程均呈一级动力学特征，符合二室模型。结论：灌胃后，叔丁基对苯二酚-硫酸结合物、叔丁基对苯二酚-葡萄糖醛酸结合物在大鼠体内达到峰值浓度的时间分别为0.17～0.61h、0.23～0.74h，分布相半衰期分别为0.32～1.11h、0.26～2.60h，消除相半衰期分别为11.75～24.54h、24.42～55.78h。雄性大鼠血清中两种代谢物的浓度显著高于雌性大鼠。两种代谢物在大鼠体内的暴露浓度均以低于与剂量呈正比的方式增加，随着剂量的升高，叔丁基对苯二酚在大鼠体内的代谢饱和。

Metabolic Kinetics of Two Metabolites from Tertiary Butylhydroquinone

Objective: The metabolic kinetics of two metabolites from tertiary butylhydroquinone,tertiary butylhydroquinone-sulfate and tertiary butylhydroquinone-glucuronide were investigated in rats.Methods: The concentrations of the metabolites in the serum of rats after oral exposure of tertiary butylhydroquinone were semi-quantitatively analyzed by liquid chromatography-mass spectrometry(LC-MS).Compartment model and metabolic kinetic parameters were evaluated by practical pharmacokinetic program.Results: The serum concentration-time profiles of two metabolites could be fitted with a two-compartment model and obeyed first-order kinetics.Conclusion: After oral administration of tertiary butylhydroquinone,the peak time of tertiary butylhydroquinone-sulfate and tertiary butylhydroquinone-glucuronide in the serum of rats were 0.17-0.61 h and 0.23-0.74 h,the distribution half-lives 0.32-1.11 h and 0.2-2.60 h,and the elimination half-lives 11.75-24.54 h and 24.42-55.78 h,respectively.The concentrations of two metabolites in the serum of male rats were higher than those in female rats.The exposure of two metabolites increased in a less-than-dose-proportional manner.Moreover,the metabolism of tertiary butylhydroquinone in rats reached saturation with increasing dose.