美斯地浓磷脂复合物大鼠体内药代动力学研究

Pharmacokinetics of Mestinon-phospholipid Complex in Rats

目的研究美斯地浓磷脂复合物在大鼠体内药代动力学特征。方法健康SD雄性大鼠12只,分为2组,采用双周期交叉随机实验,分别灌胃给予美斯地浓磷脂复合物混悬液(含美斯地浓1.5mg/kg)和美斯地浓原料药(含美斯地浓1.5mg/kg),于不同时间点眼底静脉丛取血,采用高效液相色谱法测定各时间点血药浓度。采用DAS 2.1.1药动学程序对有关参数进行分析。结果美斯地浓磷脂复合物的药代动力学参数为:达峰时间(Tmax)2h,峰浓度(Cmax)22.79μg/mL,药时曲线下面积(AUC0-∞)7128.21μg.min/mL,而美斯地浓原料药为:Tmax2h,Cmax6.00μg/mL,AUC0-∞1772.36μg.min/mL,美斯地浓磷脂复合物相对生物利用度是原料药的410.98%。结论美斯地浓磷脂化后能明显提高其口服生物利用度。

Objective To determine the pharmacokinetics characteristics of mestinon-phospholipid complex （PBPLC） in rats. Methods This study adopted a single-dose, randomized, open-label, two-period crossover trial design. Twelve healthy rats were randomly divided into two groups. One group was orally administered with mestinon-phospholipid complex, and the other group was orally administered with reference mestinon solution （1.5 mg/kg of mestinon）. The plasma concentrations of the drugs in ophthalmic vein bloods were determined using HPLC. The pharmacokinetic parameters were calculated with the aid of DAS2. 1. 1 software. Results Pharmacokinetic parameters of mestinon-phospholipid complex were Tmax 2 h, Cmax 22. 79 μg·min/mL and AUC0-∞ 7128.21 μg·min/mL, which were different from those of free mestinon Tmax 2 h, Cmax 6. 00 btg/mL and AUC0-∞ 1772.36μg·min/mL. The relative bioavailability of mestinon-phospholipid complex was 410.98 % of free mestinon. Conclusion The oral bioavailability of mestinon increases remarkably when administered as mestinon- phospholipid complex.