中国健康受试者中特拉唑嗪的安全性分析

Safety analysis of terazosin in Chinese healthy subjects

目的研究仿制盐酸特拉唑嗪胶囊与原研盐酸特拉唑嗪胶囊在中国健康受试者中的安全性,探讨用药后不良事件的影响因素。方法68例健康受试者,分为空腹、餐后各34例,分别于空腹、餐后状态下单次口服仿制药或原研药盐酸特拉唑嗪2 mg后进行随机、开放、两周期、双交叉试验。收集试验期间发生的所有不良事件(AE),分析与药物相关不良事件(CAE)的构成比与发生率,比较空腹或餐后状态下、服用仿制药或原研药受试者发生CAE的差异。结果有41例受试者(60.29%)发生100例次CAE。其中,33例受试者(48.53%)服用仿制药后发生50例次CAE,24例受试者(35.29%)服用原研药后发生50例次CAE。发生率≥10%的CAE依次为:低血压(38.24%)、头晕(16.18%)与脉搏增快(14.71%)。与原研药相比,仿制药空腹或餐后状态下给药后发生各类CAE的发生时间、持续时间比较,差异无统计学意义(P>0.05)。与空腹试验组相比,服用仿制药或原研药的受试者在餐后试验组发生低血压事件后的持续时间延长(P<0.05);服用仿制药的受试者在餐后试验组发生脉搏增快事件的时间缩短(P<0.05)。结论人体生物等效性试验中的不良事件主要来源于药物本身的安全性风险,食物可能影响特拉唑嗪的药物安全性。

Objective To investigate the safety of the generic terazosin hydrochloride capsules and the original terazosin capsules in Chinese healthy subjects,and explore the influencing factors of adverse events after medication.Methods A randomized,open,two-period,double-crossover trial was conducted in 68 healthy subjects after a single oral administration of generic drug or original drug(2 mg)under fasting and postprandial conditions,34 cases each on an empty stomach and postprandial.All adverse events(AE)during the experimental period were collected.The composition ratio and incidence rate of correlated AE(CAE)were analyzed.The differences of CAE between generic and original drugs in fasting or postprandial state were compared.Results One hundred CAEs occurred in 41 volunteers and the incidence rate was 6029%.Among them,33 subjects(4853%)experienced 50 cases of CAEs after taking generic drugs,and 24 subjects(3529%)experienced 50 cases of CAEs after taking reference drugs.The main CAE with an incidence rate≥10%were:hypotension(3824%),dizziness(1618%),and elevated arm pulse(1471%).Compared with reference drug,there was no significant difference in the occurrence time and duration of various CAEs under fasting or fed conditions(P>0.05).However,compared to the fasting test group,the duration of hypertensive events in the postprandial group was prolonged in subjects taking generic or reference drugs(P<0.05).The duration of pulse acceleration events in the postprandial group was shortened for subjects taking generic drugs(P<0.05).Conclusions Adverse events in human bioequivalence test mainly come from the safety risk of the drug itself.Food may affect the drug safety of terazosin.