盐酸戊乙奎醚片在健康人体内的药动学和生物利用度  

Pharmacokinetics and Relative Bioavailability of Penehyclidine Hydrochloride Tablet in Healthy Subjects

作　　者：胡婷婷[1] 雍小兰[1] 冯仕银[1] 黄娟[1] 李楠[1] 王蓝天[1] 康辉[1] 

机构地区：[1]成都军区总医院临床药学科,成都610083

出　　处：《中国药学杂志》2016年第10期831-835,共5页Chinese Pharmaceutical Journal

摘　　要：目的研究盐酸戊乙奎醚单次口服后在健康人体内的药动学和生物利用度。方法采用开放、随机、交叉试验设计。药动学及生物利用度实验分别选择符合入选标准的健康成年受试者12和20例,均男、女各半。单次口服药动学试验按ABC、BCA、CAB 3种给药序列随机分配受试者,每个序列组4例;该试验完成后第14天进行多次口服药动学试验,连续给药7 d。生物利用度分析按BD、DB 2种给药序列随机分配受试者,每个序列组10例。按规定时间采集血样和尿样,采用液相色谱串联质谱进行样本分析。结果 11例受试者完成药动学试验。在0.4~0.8 mg的实验剂量范围内,单次口服的盐酸戊乙奎醚片血药浓度-时间曲线呈剂量依赖性增长。血浆和尿样盐酸戊乙奎醚的线性范围分别是0.1~8 ng·mL^(-1),1~100 ng·mL^(-1)。方法准确度均在85%~115%内。多次给药后,ρ_(max)和AUC比单次给药明显增加(P<0.01),Vd和CL显著降低(P<0.01)。盐酸戊乙奎醚片的相对生物利用度为(72.44±21.03)%。盐酸戊乙奎醚在健康受试者体内以原药形式经泌尿系统的平均累积排泄率占给药剂量的(4.98±1.10)%。结论盐酸戊乙奎醚口服后在中国健康人体内具有线性药动学特征,并以泌尿系统外途径或代谢物形式排出。OBJECTIVE To explore pharmacokinetics and relative bioavailability of penehyclidine hydrochloride in healthy subjects. METHODS This study was an open,randomized and cross-over trial design. Twelve healthy subjects were randomized to receive pharmacokinetic analysis which were performed according to the order of ABC,BCA and CAB,and then pharmacokinetic trial of multiple dose was performed following penehyclidine hydrochloride. Twenty healthy subjects were selected to receive bioavailability study following an order of BD or DB. Blood and urine samples were collected at prescribed time and then investigated by LC-MS / MS.RESULTS The 11 of 12 cases finished the pharmacokinetic trial. The lineare ranges of penehyclidine hydrochloride in plasma and urine were 0. 1- 8 ng·mL^-1,1- 100 ng·mL^-1,respectively and accuracy of the method was within 85%- 115%. The concentration-time curve of penehyclidine hydrochloride was dose dependent within the ranges of 0. 4- 0. 8 mg after oral administration. ρmaxand AUC were significantly increased（ P〈0. 01）,Vd and CL were significantly decreased（ P〈0. 01） following multiple dose. The relative bioavailability of penehyclidine hydrochloride was（ 72. 44 ± 21. 03） %. The average cumulative excretion rate of penehyclidine hydrochloride with original form accounted for（ 4. 98 ± 1. 10） % of the total administered dose. CONCLUSION The characteristic of linear pharmacokinetics of penehyclidine hydrochloride is performed in healthy subjects after oral administration. Its excretion is mostly via non-urinary system or other metabolites.

关 键 词：盐酸戊乙奎醚 液相色谱串联质谱 药动学 相对生物利用度 

分 类 号：R969.1[医药卫生—药理学]