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选用体重20kg左右的大×长二元健康阉公猪8头,按双周期、双交叉试验设计,进行静脉注射及内服沃尼妙林(10.5mg/kg)的药代动力学研究。采用液相色谱-串联质谱法测定猪血浆中沃尼妙林的浓度,用3P97药代动力学程序处理血浆药物浓度-时间数据。结果,健康猪静脉注射给药的药时数据适合一级吸收二室模型,主要药代动力学参数为:t1/2α=0.21h±0.07h,t1/2β=3.09h±1.09h,Vd=3.64L/kg±0.43L/kg,CLB=0.83L/(kg·h)±0.29L/(kg·h),AUC=12.93mg/L·h±4.57mg/L·h。健康猪内服给药的药时数据适合一级吸收一室开放模型,主要药代动力学参数为:t1/2ka=0.76h±0.05h,t1/2kel=2.19h±0.31h,tmax=1.70h±0.04h,Cmax=1.35μg/mL±0.06μg/mL,AUC=7.34mg/L·h±0.52mg/L·h,F=56.62%±3.75%。结果表明,沃尼妙林在健康猪体内的药代动力学特征是:内服吸收迅速,血药浓度达峰时间短,药物峰浓度高,绝对生物利用度较高,但有效血药浓度维持时间短,药物消除较快。
Eight healthy male barrows with a size of about 20 kg and a length of about 2 kg were selected for pharmacokinetic study on intravenous injection and oral warfarin (10.5 mg / kg) according to a double-cycle, double-crossover design. The plasma concentrations of von Molin were determined by liquid chromatography-tandem mass spectrometry (HPLC-MS / MS), and the plasma drug concentration-time data were processed by the 3P97 pharmacokinetic program. The results showed that the data of healthy pigs administered intravenously were suitable for the first-order absorption two-compartment model. The main pharmacokinetic parameters were: t1 / 2α = 0.21h ± 0.07h, t1 / 2β = 3.09h ± 1.09h, Vd = 3.64 L / kg ± 0.43 L / kg, CLB = 0.83 L / (kg · h) ± 0.29 L / (kg · h), AUC = 12.93 mg / L · h ± 4.57 mg / L · h. Pharmacokinetic parameters of healthy pigs for oral administration are suitable for the first-order absorption one-compartment open model. The main pharmacokinetic parameters are: t1 / 2ka = 0.76h ± 0.05h, t1 / 2kel = 2.19h ± 0.31h, tmax = 1.70h ± 0.04 h, Cmax = 1.35 μg / mL ± 0.06 μg / mL, AUC = 7.34 mg / L · h ± 0.52 mg / L · h, F = 56.62% ± 3.75%. The results showed that the pharmacokinetic characteristics of Wane Miaolin in healthy pigs were: rapid oral administration, short peak plasma concentration, high peak drug concentration and high absolute bioavailability, but the effective plasma concentration maintenance time Short, fast elimination of drugs.