HMS-01在大鼠体内的药动学研究

目的研究HMS-01在大鼠体内的药动学,为后续研究提供支持。方法采用液相色谱-串联质谱(LCMS/MS)技术,建立灵敏、特异的测定血浆等生物样品中HMS-01浓度的分析方法,用建立的方法开展HMS-01在大鼠体内药动学研究。在SD大鼠上分别进行了1个剂量单次灌胃给药、1个剂量单次静注给药的药动学研究,以获得基本药动学参数。结果大鼠静脉注射1 mg/kg的HMS-01后,雄性与雌性大鼠血浆浓度-时间曲线下面积(AUC0-t)分别为221和409 ng·h/ml,平均清除率分别为4.53和2.41 L/h·kg,平均血浆消除半衰期分别为0.786和1.27 h,表观分布容积分别为5.13和3.82 L/kg。灌胃给予30 mg/kg的HMS-01后,在大鼠体内血浆浓度达峰时间tmax为1.17 h,达峰浓度cmax为1243 ng/ml,消除半衰期(t1/2)为2.00 h。雄、雌大鼠AUC0-t分别为2271和8529 ng·h/ml,生物利用度分别为34.3%和69.5%。结论HMS-01在大鼠体内的药动学过程存在显著的性别差异,口服吸收较好,雌性大鼠的生物利用度远高于雄性。

Pharmacokinetics of HMS-01 in rats

Objective To study the pharmacokinetics of HMS-01 in rats and provide support for subsequent study.Methods A sensitive and specific method for the determination of HMS-01 in plasma and other biological samples was established by LC-MS/MS. The pharmacokinetics of HMS-01 in rats was studied by the established method. The pharmacokinetics of one dose of single intragastric administration and one dose of single intravenous administration in SD rats were studied, and the basic pharmacokinetic parameters were obtained.Results After intravenous injection of 1 mg/kg HMS-01, the area under the plasma concentration-time curve AUC_0-t of male and female rats was 221 ng·h/ml and 409 ng·h/ml, respectively. The average clearance rates were 4.53 L/h·kg and 2.41 L/h·kg, respectively. The average plasma elimination half-lives were 0.786 h and 1.27 h, and the apparent distribution volume was 5.13 L/kg and 3.82 L/kg, respectively. After intragastric administration of 30 mg/kg HMS-01, the peak time of plasma concentration in rats was 1.17 h, the peak concentration of C_max was 1 243 ng/ml, and the elimination half-life t_1/2 was 2.00 h. The AUC_0-t of male and female rats was 2 271 and 8 529 ng·h/ml respectively, and their bioavailability was 34.3% and 69.5% respectively.Conclusion The pharmacokinetics of HMS-01 in rats has significant gender differences. It is well absorbed orally, and the bioavailability of HMS-01 in females is much higher than that in males.