非索非那定胶囊体外溶出度及在犬体内药动学评价

摘要

Objective To evaluate in vitro release behavior of fexofenadine capsules, establish a LG-MS/MS method for the content determination of fexofenadine and study its pharmacokinetics in Beagle dogs. Methods The release behavior was evaluated by using a cup method in fourmedia; a LG-MS/MSmethod was used to determine drug concentration after a single dose of administration of tablets or capsules in six dogs; pharmacokinetic parameters were calculated with the DAS2. 1.1 program. Results The two preparations showed good release behavior the AUQ0-t of fexofenadine capsules and tablets were(20. 00± 7.48) and(16.42±9.37) mg · L-1· h, AUC0-t were(20. 30±8.08) and(16. 68±9.44) mg· L-1· h, t1/2 were(3.10±1.60) and(4.54±2.03) h, tmax were(1.58±0.49) and(1.67±0.68) h, and Cmax were(4.24±1.69) and(3.68±1. 89) mg·L-1, respectively Conclusion The capsules and tablets of fexofenadine present similar release behavfor in vitro. No obvious difference has been found between the main pharmacokinetic parameters of them, which suggests they would have the same therapeutic efficacy%目的 评价非索非那定胶囊的体外溶出度,建立犬血浆中非索非那定的液质联用(LC-MS/MS)测定法,并研究其在犬体内的药动学特性.方法 采用大杯法在4种不同介质中测定非索非那定溶出度;6只比格(Beagle)犬分别单剂量灌胃给予非索非那定胶囊或非索非那定片各120 mg,采用LC-MS/MS法测定血浆非索非那定浓度,使用DAS 2.1.1程序进行药动学参数计算.结果 两种制剂体外溶出度良好;非索非那定胶囊剂及片剂的浓度-时间曲线下面积(AUC0-t)分别为(20.00±7.48)及(16.42±9.37) mg·L-1·h,AUC0-∞分别为(20.30±8.08)及(16.68±9.44) mg·L-1·h,半衰期(t1/2)分别为(3.10±1.60)及(4.54±2.03) h,达峰时间(tmax)分别为(1.58±0.49)及(1.67±0.68)h,峰浓度(Cmax)分别为(4.24±1.69)及(3.68±1.89) mg·L-1.结论 非索非那定胶囊和片剂在体外有相似溶出度,两种制剂的主要药动学参数无明显差异,预示临床有相同疗效.