非索伪麻缓释片在人体内的药动学研究

Pharmacokinetics study of Fexofenadine/Pseudoephedrine Sustained-release Tablets in healthy Chinese volunteers

目的研究非索伪麻缓释片单次及多次给药后非索非那定和盐酸伪麻黄碱在人体内的药代动力学参数,并与普通制剂那敏伪麻胶囊比较,判断盐酸伪麻黄碱的缓释特征。方法 12名受试者在单次给药试验完成后进行多次给药试验;受试制剂与参比制剂的药代动力学比较研究采用双周期交叉试验设计。采用LC/MS/MS法测定受试血浆中非索非那定和盐酸伪麻黄碱的质量浓度。结果受试者单次口服非索伪麻缓释片后,测得非索非那定的Cmax,tmax,AUC0-t和t1/2分别为（133±44）μg·L-1,（2.2±1.4）h,（1 088±288）μg·h·L-1和（9.97±2.14）h;盐酸伪麻黄碱的Cmax,tmax,AUC0-t和t1/2分别为（319±47）μg·L-1,（4.0±1.4）h,（4 046±857）μg·h·L-1和（5.81±0.93）h。多次口服非索伪麻缓释片后,测得非索非那定的Cmax,tmax,AUC0-t和t1/2分别为（464±95）μg·L-1,（1.1±0.4）h,（3 005±425）μg·h·L-1和（9.81±2.12）h;盐酸伪麻黄碱的Cmax,tmax,AUC0-t和t1/2分别为（381±54）μg·L-1,（3.1±1.0）h,（4 608±802）μg·h·L-1和（5.78±0.47）h。非索伪麻缓释片中盐酸伪麻黄碱AUC和Cmax的90%置信区间分别为那敏伪麻胶囊中盐酸伪麻黄碱相应参数的99.6%~119.3%和77.6%~94.7%,tmax显著延长。结论口服非索伪麻缓释片后,非索非那定吸收较快,而伪麻黄碱则表现出缓释特征,但吸收程度与普通制剂相同。非索非那定多次给药后血药质量浓度明显高于单次给药。

Objective To study the pharmacokinetics of fexofenadine and pseudoephedrine hydrochloride in human after a single and multiple oral dose of Fexofenadine/Pseudoephedrine Sustained-release Tablets and to assess the sustain-release characteristics of pseudoephedrine hydrochloride compared with the conventional preparation of pseudoephedrine hydrochloride and Chlorphenamine Maleate Capsules.Methods An oral single dose and multiple doses of Fexofenadine/Pseudoephedrine Sustained-release Tablets were given to 12healthy volunteers sequentially,respectively.A two-period crossover design was used in the comparison study of the conventional formulation and the sustain-release formulation.An LC/MS/MS method was used for the determination of fexofenadine and pseudoephedrine hydrochloride in human plasma.Results After a single dose administration of Fexofenadine/Pseudoephedrine Sustained-release Tablets,the main pharmacokinetic parameters were as follows：Cmax（133±44）μg·L-1,tmax（2.2± 1.4）h,AUC0-t（1 088±288）μg·h·L-1 and t1/2（9.97±2.14）h for fexofenadine and Cmax（319±47）μg·L-1,tmax（4.0±1.4） h,AUC0-t（4 046±857）μg·h·L-1 and t1/2（5.81±0.93）h for pseudoephedrine hydrochloride.After the multiple doses administration of Fexofenadine/Pseudoephedrine Sustained-release Tablets,the main pharmacokinetic parameters were as follows：Cmax（464±95）μg·L-1,tmax（1.1±0.4）h,AUC0-t（3 005±425）μg·h·L-1 and t1/2（9.81±2.12）h for fexofenadine and Cmax（381 ±54）μg·L-1,tmax（3.1±1.0）h,AUC0-t（4 608±802）μg·h·L-1 and t1/2（5.78±0.47）h for pseudoephedrine hydrochloride.The 90%confidence interval of AUC and Cmax of pseudoephedrine hydrochloride of the sustained-release formulation were 99.6%-119.3%and 77.6%-94.7%,respectively.The tmax was prolonged significantly.Conclusion After administration of Fexofenadine/Pseudoephedrine Sustained-release Tablets,the absorption rate of fexofenadine was rapid and the pseudoephedrine hydrochloride showed the sustained-released characteristics.However the same absoption tendency as the conventional formulation was showed.The concentrations of fexofenadine in plasma of multiple doses administration were significantly higher than that of single dose administration.