对乙酰氨基酚在大鼠体内药动学研究

Study on Pharmacokinetics of Paracetamol in Rats

目的应用反相高效液相色谱法(RP-HPLC)测定大鼠血浆中对乙酰氨基酚浓度,研究单剂量口服不同剂量对乙酰氨基酚片在大鼠体内的药代动力学。方法3组SD大鼠分别按体重单剂量口服对乙酰氨基酚片300 mg/kg、600 mg/kg、1 200 mg/kg后,采用RP-HPLC测定血浆中药物的浓度,绘制血药浓度-时间曲线,计算其药代动力学参数。结果3个剂量组的对乙酰氨基酚药-时曲线均符合口服吸收的一级动力学二室模型,主要药代动力学参数:Tmax分别为(0.78±0.17)h、(1.07±0.12)h、(1.19±0.12)h;Cmax分别为(158.99±26.08)μg/ml、(226.26±20.38)μg/ml、(402.95±86.46)μg/ml;T1/2kα分别为(0.24±0.09)h、(0.39±0.11)h、(0.43±0.14)h;T1/2ke分别为(3.78±0.33)h、(3.66±0.32)h、(4.33±0.47)h;AUC0→24分别为(718.71±143.03)μg.h-1.ml-1、(1 578.53±246.76)μg.h-1.ml-1、(3 734.67±665.58)μg.h-1.ml-1;AUC0→∞分别为(757.16±155.29)μg.h-1.ml-1、(1 594.61±247.11)μg.h-1.ml-1、(3 847.99±692.03)μg.h-1.ml-1。结论所建立RP-HPLC法能够准确地测定对乙酰氨基酚血药浓度,能满足药代动力学的研究需求;低剂量组和中剂量组的药代动力学过程基本相似,但高剂量组则与上述两组则有所不同,这可能与其剂量过高有关。

Objective To apply the reversed-phase high performance liquid chromatography（RP-HPLC）method for determination of plasma drug concentration of paracetamol in rats,to investigate the pharmacokinetics in rats after different doses of a single oral paracetamol tablet.Methods After three groups of rats were given an oral paracetamol tablet in a single oral dose of 300 mg/kg,600 mg/kg,1 200 mg/kg by weight separately,the concentrations of paracetamol in plasma were determined by RP-HPLC,and then the blood concentration-time curves was draw and the pharmacokinetic parameters was calculated.Results The plasma concentration-time curves of paracetamol were fitted to a two-compartment model with first order absorption in rats after a oral paracetamol tablet in single dose（300 mg/kg,600 mg/kg,1 200 mg/kg,respectively）.The main pharmacokinetic parameters of paracetamol in three groups rats were as follows.Tmax were（0.78±0.18）h,（1.07±0.12）h and（1.19±0.12）h.Cmax were（158.99±26.08）μg/ml,（226.26±20.38）μg/ml and（402.95±86.46）μg/ml.T1/2kα were（0.24±0.09）h,（0.39±0.11）h and（0.43±0.14）h.T1/2ke were（3.78±0.33）h,（3.66±0.32）h and（4.33±0.47）h.AUC0→24 were（718.71±143.03）μg·h^-1·ml^-1 578.53±246.76）μg·h^-1·ml^-1 and（3 734.67±665.58）μg·h^-1·ml^-1C0→∞ were（757.16±155.29）μg·h^-1·ml^-1 594.61±247.11）μg·h^-1·ml^-1d（3 847.99±692.03）μg·h^-1·ml^-1nclusion The RP-HPLC method could be suitable for the determination of rats serum paracetamol and pharmacokinetics researches.The main pharmacokinetic parameters of paracetamol between the low-dose group and the medium-dose group were basically the same,different from those of the high dose group,which might be related to the high dosage.