马来酸氟吡汀滴丸的药动学研究

Study on the pharmacokinetics of flupirtine maleate dropping pills

目的:以市售马来酸氟吡汀胶囊为参比制剂,评价自制马来酸氟吡汀滴丸的相对生物利用度。方法:采用高效液相色谱法测定马来酸氟吡汀缓释滴丸和胶囊剂单剂量灌胃(ig)给药后大鼠的血药浓度变化,DAS 2.0软件计算分析其药动学参数和相对生物利用度。结果:马来酸氟吡汀自制缓释滴丸与市售胶囊的药动学参数间均有显著性差异,其中:Tmax分别为(3.400±0.548)和(2.200±0.447)h;Cmax分别为(3.996±0.199)和(3.236±0.141)μg·m L-1,在胶囊剂达峰时间T2.2h处Cmax(滴丸)远大于Cmax(胶囊);AUC0~∞分别为(48.503±2.749)和(33.889±3.195)μg·m L-1·h;MRT分别为(9.212±1.752)和(7.160±0.563)h,马来酸氟吡汀缓释滴丸相对于胶囊剂的生物利用度为(144.388±18.400)%。结论:同样剂量给药,马来酸氟吡汀滴丸较市售胶囊血浓度高、起效快、药效作用时间长、生物利用度高,可以为马来酸氟吡汀滴丸的药效学实验及缓释制剂的研发提供参考。

Objective： To study the relative bioavailability and bioequivalence of flupirtine maleate sustainedrelease dropping pills and flupirtine maleate commercial capsules. Methods： SD rats were used as experimental animals,high performance liquid chromatography was used to determine the plasma concentrations in rats after given single oral dose of the flupirtine maleate sustained-release dropping pills and commercial capsules.Pharmacokinetic parameters were calculated with DAS 2. 0 software. Results： The main pharmacokinetic parameters for flupirtine maleate sustained-release dropping pills and commercial capsules were as follows： Tmax（ 3. 400 ±0. 548） and（ 2. 200 ± 0. 447） h; Cmax（ 3. 996 ± 0. 199） and（ 3. 236 ± 0. 141） μg·m L-1. In peak time at T2. 2hof capsules,the Cmaxof drop pill is far greater than Cmaxof capsules; AUC0 - ∞（ 48. 503 ± 2. 749） and（ 33. 889 ±3. 195） μg·m L^-1·h; MRT（ 9. 212 ±1. 752） and（ 7. 160 ±0. 563） h,respectively. The mean relative bioavailability of flupirtine maleate sustained-release dropping pills to capsules was（ 144. 388 ± 18. 400） %. Conclusion： At the same dose,the flupirtine maleate dropping pills were more excellent in bioavailability and absorption than capsules.The results can provide reference for the pharmacodynamic experiment of flupirtine maleate dropping pills and the research of sustained-release preparations.