乙酰半胱氨酸颗粒在健康人体的生物等效性研究  

Study on Bioequivalence of Acetylcysteine Granules in Chinese Healthy Volunteers

作　　者：李杰[1] 刘明周[2] 黎维勇[1] 贾萌萌[1] 周颖[1] 李虎群[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院药剂科,武汉430022 [2]武汉大学基础医学院,武汉430071

出　　处：《医药导报》2015年第8期1014-1018,共5页Herald of Medicine

摘　　要：目的建立人血浆乙酰半胱氨酸浓度测定方法,研究乙酰半胱氨酸颗粒在健康人体内的相对生物利用度与生物等效性。方法采用二制剂三周期自身对照完全三交叉试验设计,其中每位受试者有一周期不服药,健康男性受试者24例分别单剂量口服乙酰半胱氨酸受试制剂或参比制剂0.6 g。高效液相色谱串联质谱法测定血浆乙酰半胱氨酸浓度,应用DAS 3.0版统计软件计算药动学参数并评价两种制剂生物等效性。结果单剂量口服乙酰半胱氨酸颗粒受试制剂和参比制剂0.6 g的主要药动学参数:AUC0→t分别为(8 547.64±2 860.04)和(8 783.07±4 042.10)μg·h·L-1;AUC0→∞分别为(9 481.64±3 444.76)和(9 540.51±4 239.30)μg·h·L-1;Cmax分别为(1 994.39±726.42)和(2 090.27±885.46)μg·L-1;tmax分别为(1.18±0.60)和(1.13±0.53)h;t1/2分别为(8.60±3.76)和(7.75±5.01)h;相对生物利用度以AUC0→t和AUC0→∞计算分别为(107.00±43.30)%和(106.50±40.10)%。结论乙酰半胱氨酸颗粒两种制剂具有生物等效性。Objective To establish an analytical method for assessing acetylcysteine in human plasma and study the relative bioavailability and bioequivalence of aeetylcysteine granules in Chinese healthy volunteers. Methods In the randomized crossover study, 24 healthy male volunteers received a single oral dose of 0.6 g test acetylcysteine granules, reference acetylcysteine granules or no medication. The plasma concentration of acetylcysteine was determined by LC-MS/MS. Pharmacokinetic parameters were calculated and bioequivalence of two preparations were evaluated by DAS3.0 software. Results The main pharmaeokinetic parameters of the test and reference preparations were as follows： AUC0→∞, was （8 547.64 ± 2 860.04） and （8 783.07±4 042.10） μg·h·L-1, respectively; AUC0→∞ was （9 481.64±3 444.76） and （9 540.51± 4 239.30）μg·h·L-1 , respectively; Cmax was （ 1 994.39±726.42） and （2 090.27±885.46） μg·L^-1 , respectively; tmax was （1.18±0.60） and （1.13±0.53） h, respectively; t1/2 was （8.60±3.76） and （7.75±5.01） h, respectively. The relative bioavailability F0→ttand F0→∞ was （ 107.00±43. 30）% and （ 106. 50±40. 10）%, respectively. Conclusion The results of statistical analysis indicate that the test and reference formulations are bioequivalent. KEY WORDS Aeetyleysteine granules ; Bioavailability, relative ; Bioequivalence ; Liquid chromatography-tandem mass spectrometry

关 键 词：乙酰半胱氨酸颗粒 生物利用度 相对 生物等效性 液相色谱串联质谱法 

分 类 号：R974.1[医药卫生—药品] R969.1[医药卫生—药学]