毛兰素注射液在大鼠体内药动学研究

目的阐明毛兰素注射液在SD大鼠体内药动学规律。方法 SD大鼠分别单次和隔天、每隔一个半衰期一次多剂量静脉注射毛兰素注射液。采用高效液相色谱-质谱联用（HPLC-MS）测定大鼠静脉注射后不同时间大鼠血浆中毛兰素的血药浓度。结果大鼠单次静脉注射25,50,100mg·kg-1毛兰素注射液的主要药动学参数为：T1/2β分别为3.66,3.75,3.89h;AUC0-12分别为1453.0,3041.6,6731.6ng·mL-1·h;AUC0-∞分别为1462.0,3077.3,6788.7ng·mL-1·h;Vd分别为11.67,10.37,3.38L·kg-1;CL分别为0.049,0.089,0.024L·kg-1·h-1;MRT分别为0.18,0.28,0.21h;50mg·kg-1剂量的毛兰素注射液隔日给药5次其药动学参数与单次给药相近;而50mg·kg-1剂量的毛兰素注射液每隔一个半衰期一次给药5次的T1/2β为5.43h,AUC（S0）（0-t）为9800.8ng·mL-1·h。结论毛兰素注射液在大鼠体内的动力学过程与剂量相关,毛兰素注射液单剂量给药的体内药动学符合开放型二房室模型,T1/2β与给药剂量与关,表明毛兰素在大鼠体内的消除过程符合一级动力学规律。隔日多剂量给药的消除过程亦符合一级动力学规律;而每隔一个半衰期一次多剂量给予50mg·kg-1剂量的毛兰素其在大鼠体内则呈非线性消除。

Pharmacokinetic Study of Erianin Fat Emulsion in Rats

OBJECTIVE To elucidate pharmacokinetics of erianin fat emulsion in rats.METHODS An HPLC-MS method was developed and used to determine the rats plasma concentration of erianin after intravenous injection at single,and dosage multiple dosages which with each two days and each half elimination time（t1/2） a time administration.RESULTS The parameters of single dosage as 25,50,100 mg·kg-1 of erianin in rats：T1/2β values were 3.66,3.75 and 3.89 h.AUC0-12 values were 1 453.0,3 041.6,6 731.6 ng·mL-1·h.AUC0-∞ values were 1 462.0,3 077.3,6 788.7 ng·mL-1·h.Vd values were 11.67,10.37 and 3.38 L·kg-1.CL values were 0.049,0.089,0.024 L·kg-1·h-1.MRT values were 0.18,0.28,0.21 h,respectively.The parameters of erianin multiple dosages with 50 mg·kg-1 administration each two days were similar as the single dosage.However,the T1/2β value prolonged to 5.43 h,the AUC（S0）（0-t） elevated to 9 800.8 ng·mL-1·h,while multiple dosage of 50 mg·kg-1 each half elimination time.CONCLUSION The pharmacokinetics of erianin fat emulsion with single dosage administration in rats had dose-concentration linearity,the T1/2β values had no change within the dose range.It suggested that erianin fat emulsion pharmacokinetics was in accordance with two-compartment open model,and its elimination in rats obey with linear kinetics.However,administration with each t1/2 a time at the dose of 50 mg·kg-1 of erianin,its elimination obeyed nonlinear kinetics.