甲基叔丁醚在大鼠体内的药物动力学(英文)

甲基叔丁醚(MTBE)是在临床试验中的一种胆石溶解剂。体内研究表明它对溶解许多胆囊结石和一些胆道结石有效。为分析其效力和毒性,本文用气相色谱内标法测定了MTBE及主要代谢物甲醇在大鼠的血清浓度,并研究了MTBE的药物动力学。大鼠igMTBE0.379mg/kg后的MTBE血清浓度的变化符合一室开放模型。其药物动力学参数如下:k_a为3.7 h~(-1),k为0.57 h~(-1),T_(1/2ka)为0.32 h,T_(1/2k)为1.26 h,T_(max)为0.9h,C_(max)为5.9μg/ml,AUC_(0-6h)为16.4μg·h·ml~(m-1)。甲醇血清浓度在igMTBE后显示有积蓄。甲醇/MTBE的浓度比率有显著增加。结果提示在应用MTBE时,尽可能避免其吸收,且须预防甲醇毒性。

Pharmacokinetics of methyl tert-butyl ether (MTBE) in rats

MTBE is a gallstone dissolving agent in clinical trial. Preliminary results in vivo showed that MTBE is effective for the dissolution of many gallbladder stones and some bile duct stones.In this paper, a gas chromatographic method with an internal standard was used for analyses of MTBE and its main metabolite methanol in rat serum, and pharma cokinetics of MTBE was studied for the evaluation of its efficacy and toxicity. Pharmacokinetic studies showed that individual serum curves of MTBE concentration vs time were analyzed respectively following one compartment model after ig MTBE (0.379 mg / kg). The pharmacokinetic parameters are as follows: ka=3.70 h-1, k = 0.57 h1, tl/2ka = 0.32 h, t1/2k=1.26 h, tmax = 0.85 h, Cmax=5.85 μg/ml, AUC0.6h = 16.37 μg·h·ml 1.An accumulation of serum methanol concentrations was observed after ig MTBE. Ratios of serum concentrations of methanol to MTBE (μmol / μmol) during the period of taking sample time are significantly increasing. It suggests that the toxicity of methanol must be prevented when MTBE is used.