摘要
目的评价加兰他敏缓释混悬液单次和多次口服在健康人体内的药动学特征和安全性。方法将36名健康受试者分为低(8 mg)、中(16 mg)、高(24 mg)剂量组,男、女各18名。单次给药在低、中、高剂量组中共同进行,多次给药在中剂量组中进行。采用LC-MS/MS法测定血浆中加兰他敏浓度,应用Win Nonlin 6.3软件计算药动学参数,并用幂函数模型分析单次给药剂量组ρmax、AUC_(0→∞)与剂量的线性关系。用不良事件来评估安全性。结果低、中、高剂量组单次给药及中剂量组多次给药的主要药动学参数tmax分别为(5.08±2.50)、(3.73±1.47)、(3.88±1.51)、(2.98±1.57)h;ρmax分别为(21.38±3.26)、(41.74±6.51)、(53.99±9.57)、(49.95±10.18)μg·L^(-1);AUC_(0→∞)分别为(437±119)、(749±140)、(1 019±231)、(963±276)h·μg·L^(-1)。ρmax和AUC_(0→∞)随着给药剂量增加而增大,即药物呈线性消除。健康受试者不良反应主要为神经系统和胃肠系统症状。结论加兰他敏缓释混悬液日剂量在8~24 mg内呈线性药动学特征,安全性和耐受性良好。
AIM To evaluate the pharmacokinetic characteristics and safety of single-dose and multi-dose of oral galantamine sustained release suspension in healthy volunteers. METHODS Totally 36 healthy volunteers （18 males and 18 females） were divided into three parallel dose groups which were low （8 mg）, medium（16 mg） and high（24 mg） respectively. The pharmacokinetic studies of single-dose were carried out in three groups and the multi-dose was in medium dose group. The galantamine concentrations in plasma were determined by LC-MS/MS. WinNonlin 6.3 software was used to calculate the pharmacokinetic parameters. The adverse events were used to evaluate safety. RESULTS The main pharmacokinetic parameters of three single-dose groups and the multi-dose were as follows： tin=were （5.08 ±2.50）, （3.73 ±1.47）, （3.88 ±1.51） and （2.98 ±1.57） h; pmas were （21.38±3.26）, （41.74 ±6.51）, （53.99±9.57） and （49.95 ±10.18） μg·L^-1; AUC0→∞ were （437 ±119） , （749 ±140）, （1 019 ±231） and （963 ±276） h·μg·L^-1 Power function model was used to analyze linear relationship of pmax, AUC0→∞ and dosage. It showed a linear elimination. The adverse drug reactions were mainly neurological and gastrointestinal symptoms in healthy volunteers. CONCLUSION Over a range of 8 -24 mg·d ^-1, the galantamine sustained release suspension displays linear pharmacokinetic characteristics and is safety and tolerable.
作者
余一旻
李华芳
张岩
葛庆华
黄文武
刘红霞
李妍
沈一峰
YU Yimin;LI Huafang;ZHANG Yan;GE Qinghua;HUANG Wenwu;LIU Hongxia;LI Yan;SHEN Yifeng(MICT , Shanghai Mental Health Center, Shanghai 200030, China;Shanghai Modem Pharmaceutical Engineering Research Center Co. Ltd. , Shanghai 200137, China;Department of Medicine, Shanghai Modern Pharmaceutical Ltd. , Shanghai 200040 ,China;Center for Drug Clinical Research, Shanghai University of Chinese Medicine, Shanghai 201203 ,China;Shanghai Key Laboratory of Severe Mental Disorders, Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China)
出处
《中国临床药学杂志》
CAS
2018年第1期1-7,共7页
Chinese Journal of Clinical Pharmacy
基金
"重大新药创制"科技重大专项(编号2017ZX09304-020)
上海市科委产学研医项目(编号12DZ1931204)
