益母草碱及其代谢物在大鼠体内的毒代动力学研究

Toxicokinetics of Leonurine and Its Metabolite in Rats

建立了测定大鼠血浆中益母草碱(1)及其葡萄糖醛酸结合物(2)的LC-MS/MS方法。考察了大鼠单次和连续28 d灌胃给予低、中、高剂量1(200、600和2 000 mg/kg)后1和2在体内的暴露水平,绘制药-时曲线并计算毒代动力学参数。单剂量试验表明,低、中、高剂量组1的AUC分别为(1.946±0.908)、(7.002±2.759)和(26.408±11.491)mol.L-1.h,1在大鼠体内消除行为符合线性动力学模型。多剂量试验表明,低、中、高剂量组1的AUC分别为(2.987±1.089)、(9.083±3.140)和(20.178±7.484)mol.L-1.h。长期大剂量灌胃给予1,1和2均未见在大鼠体内明显蓄积,且试验过程中未见大鼠有明显的毒性反应。

A LC-MS/MS method for determination of leonurine（1） and its metabolite leonurine-O-glucuronide（2） in rat plasma was established.After single-or multiple-dose（once daily for 28 d） ig administration of 1 at low,middle and high doses,the exposure levels of 1 and 2 in rats were investigated.The concentration-time curves of 1 and 2 were drawn and the toxicokinetic parameters were calculated.The AUC of 1 for single-dose ig administration of 200,600,2 000 mg/kg were（1.946±0.908）,（7.002±2.759） and（26.408±11.491）μmol·L-1·h,respectively.The results suggested that the elimination behavior of 1 in rats accorded with linear dynamic model.The AUC of 1 for multiple-dose ig administration were（2.987±1.089）,（9.083±3.140） and（20.178±7.484）μmol·L-1·h,respectively.No significant accumulation was observed after successive large dose ig administration of 1 in rats.During the experiment there was no significant toxicity in rats.