盐酸氟桂利嗪胶囊在中国健康志愿者空腹和进食条件下的生物等效性研究  

Bioequivalence of Flunarizine Hydrochloride Capsules under Fasting and Feeding Conditions in Chinese Healthy Volunteers

作　　者：王倩 田庆云 徐永辉 董继宁 解泽康 王彦超 赵可新 Wang Qian;Tian Qingyun;Xu Yonghui;Dong Jining;Xie Zekang;Wang Yanchao;Zhao Kexin(Hebei Petrochina Central Hospital,Hebei Langfang 065000,China)

机构地区：[1]河北中石油中心医院,河北廊坊065000

出　　处：《中国药师》2022年第6期1115-1120,共6页China Pharmacist

摘　　要：目的:评价山西振东安特生物制药有限公司生产的盐酸氟桂利嗪胶囊与西安杨森制药有限公司生产的盐酸氟桂利嗪胶囊的生物等效性,为一致性评价提供依据。方法:采用随机、开放、单剂量、两制剂、两周期、两交叉给药试验设计,空腹组和高脂餐后组各入组26名受试者,所有受试者随机分为两组,每周期给药1次,每次口服给药剂量为5 mg(1粒),清洗期28 d,之后进行交叉给药。采用HPLC-MS/MS法测定健康受试者口服受试制剂(T)或参比制剂(R)后,血浆中不同时间点氟桂利嗪的血药浓度。采用WinNonlin8.2和SAS9.4版本软件,非房室模型计算各受试者的药动学参数,并进行统计分析。对受试者的临床观察指标进行安全性评价。结果:空腹组24例和高脂餐后组25例完成全部试验。空腹条件下,盐酸氟桂利嗪胶囊T和R的血药浓度达峰时间(T_(max))分别为2.50 h(1.50-5.50 h)和2.50 h(1.50-4.50 h),血药峰浓度(C_(max))分别为(21.09±6.72)ng·ml^(-1)和(20.36±5.69)ng·ml^(-1),血药浓度-时间曲线下面积(AUC_(0-72h))分别为(239.05±94.19)h·ng·ml^(-1)和(223.78±77.54)h·ng·ml^(-1);AUC_(0-t)分别为(324.73±152.96)h·ng·ml^(-1)和(298.97±130.39)h·ng·ml^(-1);AUC_(0-∞)分别为(457.12±268.55)h·ng·ml^(-1)和(366.15±172.77)h·ng·ml^(-1);半衰期(t_(1/2))分别为(180.87±153.04)h和(112.18±70.51)h。进食条件下,盐酸氟桂利嗪胶囊T和R的T_(max)分别为4.50(2.50-6.50)h和4.50(2.50-6.00)h,C_(max)分别为(30.52±10.73)ng·ml^(-1)和(30.65±8.55)ng·ml^(-1),AUC_(0-72h)分别为(269.16±71.76)h·ng·ml^(-1)和(273.30±74.83)h·ng·ml^(-1);AUC_(0-t)分别为(360.71±121.08)h·ng·ml^(-1)和(362.30±117.22)h·ng·ml^(-1);AUC_(0-∞)分别为(449.48±171.08)h·ng·ml^(-1)和(470.51±161.88)h·ng·ml^(-1);t_(1/2)分别为(131.21±60.38)h和(196.35±132.07)h。空腹和餐后状态下T、R的C_(max)、AUC_(0-72h)、AUC_(0-t)和AUC_(0-∞)均值比的90%置信区间均在(80.00%,125.00%)等效区间内。结Objective:To evaluate the bioequivalence between flunarizine hydrochloride capsules produced by Shanxi Zhendong Ante Biological Pharmaceutical Co.Ltd.and those produced by Xi’an Jansen Pharmaceutical Co.Ltd.,and to provide basis for consistency evaluation.Methods:A randomized,open,single dose,two preparations,two-cycle,and two-cross-administration trial was applied.Totally 26 subjects were enrolled in fasting group and another 26 ones were in high-fat meal group.All the subjects were randomly divided into two groups,and the drug was administered once per cycle at the dose of 5 mg.The washing period was 28 d,and after which cross-administration was performed.The plasma concentrations of flunarizine in healthy subjects at different time points after oral administration of test preparation(T)or reference preparation(R)were determined by HPLC-MS/MS.The pharmacokinetic parameters of each subject were calculated by non-atrioventricular model using WinNonlin8.2 and SAS9.4 software,and statistical analysis was conducted.The safety of the clinical observation indexes of subjects was evaluated.Results:Under fasting condition,T_(max) of flunarizine hydrochloride capsules test preparation and reference preparation was 2.50 h(1.50-5.50)h and 2.50 h(1.50-4.50)h,C_(max) was(21.09±6.72)ng·ml^(-1) and(20.36±5.69)ng·ml^(-1),AUC_(0-72h)was(239.05±94.19)h·ng·ml^(-1) and(223.78±77.54)h·ng·ml^(-1),AUC_(0-t) was(324.73±152.96)h·ng·ml^(-1) and(298.97±130.39)h·ng·ml^(-1),AUC_(0-∞)was(457.12±268.55)h·ng·ml^(-1) and(366.15±172.77)h·ng·ml^(-1),and t_(1/2) was(180.87±153.04)h and(112.18±70.51)h,respectively.Under feeding condition,T_(max) of T and R of flunarizine hydrochloride capsules was 4.50(2.50-6.50)h and 4.50(2.50-6.00)h,C_(max) was(30.52±10.73)ng·ml^(-1) and(30.65±8.55)ng·ml^(-1),AUC_(0-72h)was(269.16±71.76)h·ng·ml^(-1) and(273.30±74.83)h·ng·ml^(-1),AUC_(0-t) was(360.71±121.08)h·ng·ml^(-1) and(362.30±117.22)h·ng·ml^(-1),AUC_(0-∞) was(449.48±171.08)h·ng·ml^(-1) and(470.51±161.88)h·ng�

关 键 词：氟桂利嗪 生物等效性 高效液相色谱-质谱联用 药物动力学 安全性 

分 类 号：R969.1[医药卫生—药理学]