石杉碱甲在中国老年受试者中药动学和安全性研究  

Pharmacokinetics and Safety of Huperzine A in Chinese Elderly Subjects

作　　者：钱泓洁 张梦琪[1] 邹扬 刘淑云 王伟[2] 陈倩[1] 刘罡一[1] 刘昀[1] 余琛[1] 贾晶莹[1] QIAN Hongjie;ZHANG Mengqi;ZOU Yang;LIU Shuyun;WANG Wei;CHEN Qian;LIU Gangyi;LIU Yun;YU Chen;JIA Jingying(Central Laboratory,Shanghai Xuhui Central Hospital,Shanghai Engineering Research Center of Phase I Clinical Research&Quality Consistency Evaluation for Drugs,Shanghai 200031,China;Department of Emergency,Shanghai Xuhui Central Hospital,Shanghai 200031,China)

机构地区：[1]上海市徐汇区中心医院中心实验室上海药物Ⅰ期临床暨药物一致性评价工程技术研究中心,上海200031 [2]上海市徐汇区中心医院急诊科,上海200031

出　　处：《医药导报》2021年第6期764-767,共4页Herald of Medicine

基　　金：上海市科学技术委员会科研计划项目(18DZ2250500)。

摘　　要：目的探索石杉碱甲在中国老年受试者体内的药动学特点和安全性。方法 14例无认知功能障碍的中国老年受试者(年龄60~80岁)接受单次口服石杉碱甲0.1 mg,在给药后48 h内收集血液和尿液样本。采用液相色谱-串联质谱(LC-MS/MS)法测定生物样品中药物浓度,以获得药动学参数。在整个研究过程中,对受试者进行安全性指标和不良事件监测。结果老年受试者单次口服石杉碱甲0.1 mg后主要药动学参数:峰浓度(C_(max))(0.92±0.28) ng·mL^(-1),峰时间(t_(max))(2.61±1.67) h,血浆浓度-时间曲线下面积(AUC_((0-72h)))(15.12±4.73) ng·h·mL^(-1),AUC_((0-∞))(16.99±4.92) ng·h·mL^(-1),消除半衰期(t_(1/2))(14.38±3.87) h, 48 h累计尿液药物排泄率为34.76%。1例受试者(7.1%)发生与研究药物可能无关的轻度不良事件。结论石杉碱甲在中国老年受试者中有良好的耐受性。相比非老年健康受试者,老年受试者中石杉碱甲的吸收和消除过程相对更缓慢,暴露程度更高。Objective To investigate the pharmacokinetics and safety of huperzine A in Chinese elderly subjects. Methods Fourteen subjects aged 60-80 years, without cognitive impairment, received a single dose of 0.1 mg huperzine A.Blood and urine samples were collected to measure the pharmacokinetic profiles within 48 h after the drug administration.A validated LC-MS/MS method was used to determine drug concentration in biological samples.Safety parameters including adverse events were monitored throughout the study. Results The maximum observed concentration(C_(max)) in plasma was(0.92±0.28) ng·mL^(-1);t_(max) was(2.61±1.67) h;AUC_((0-72 h)) was(15.12±4.73) ng·h·mL^(-1)and AUC_((0-∞)) was(16.99±4.92) ng·h·mL^(-1). Elimination half-life(t_(1/2)) was(14.38±3.87) h.Accumulated excretion rate was 34.76% within 48 h after huperzine A administration.One case subject(7.1%) reported mild AE which were unlikely to be related to the study drug. Conclusion The results showed that huperzine A was well tolerated in Chinese elderly subjects.Pharmacokinetic data demonstrated a relative slower process of absorption and elimination, and higher exposure of huperzine A in the elderly population compared to non-elderly population.

关 键 词：石杉碱甲 老年人 药动学 安全性 阿尔茨海默病 

分 类 号：R971.1[医药卫生—药品] R969.1[医药卫生—药学]