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对莫达非尼(modafinil,MOD)在小鼠体内的药动学和药效学进行联合研究,以阐明其关联性,为临床合理用药提供依据。以莫达非尼120 mg.kg-1对小鼠灌胃给药,采集给药后不同时间点血浆样本,用HPLC检测血浆药物浓度,分析平均血药浓度经时变化并计算药动学参数。以小鼠自主活动计数为药效学指标,观测MOD 120 mg.kg-1灌胃给药后不同时间段内小鼠自主活动量(计数)的变化,分析与血浆药物浓度变化的相关性。结果显示,MOD在小鼠体内药动学过程符合二室模型,t1/2α,t1/2β,tmax,Cmax,AUC0-∞分别为0.42 h,3.10 h,1.00 h,41.34 mg.L-1和142.22 mg.L-1.h。MOD使小鼠自主活动明显增多,持续约4 h,且与血浆药物浓度呈同步变化,二者间存在明显的相关性。
To study the pharmacokinetics and pharmacodynamics of modafinil (MOD) in mice to clarify its association and provide a basis for clinical rational drug use. The mice were given intragastric administration of modafinil 120 mg.kg-1, the plasma samples were collected at different time points after administration, the plasma drug concentration was measured by HPLC, the mean plasma concentration was analyzed and the pharmacokinetic parameters were calculated . The autonomic activity counts in mice were taken as pharmacodynamic indexes. The changes of autonomic activity (counts) in different periods of time after MOD 120 mg · kg-1 administration were observed, and the correlations with changes of plasma drug concentration were analyzed. The results showed that the pharmacokinetics of MOD in mice accorded with two-compartment model. The t1 / 2α, t1 / 2β, tmax, Cmax and AUC0-∞ were 0.42 h, 3.10 h, 1.00 h and 41.34 mg.L- 142.22 mg.L-1.h. MOD significantly increased autonomic activity in mice, lasting about 4 h, and the concentration of plasma drug showed a synchronous change, there is a clear correlation between the two.