健康志愿者单次、多次口服美金刚片的人体药动学  

Pharmacokinetics of single-oral dose and multiple-oral dose of memantine tablets in human volunteers

作　　者：杨明威[1] 蒋俊毅[1] 钱薇[1] 林慧[1] 肖大伟[1] 张宜山[2] 陈卫东[2] 陶菲[2] 

机构地区：[1]南京大学医学院附属鼓楼医院Ⅰ期临床试验研究室,江苏南京210008 [2]江苏奥赛康药业股份有限公司,江苏南京211112

出　　处：《中国新药与临床杂志》2013年第4期279-284,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的研究健康志愿者单次和多次口服美金刚片的药动学。方法 36名健康受试者分为三组分别服用盐酸美金刚片5、10、20 mg;5 mg组为多次给药组,多次给药方案为5 mg q48 h×7 d。以HPLC-MS/MS方法测定美金刚的血药浓度。以BAPP 3.0计算其药动学参数。结果美金刚片5、10和20 mg单次口服,cmax为(9.32±2.41)、(20.40±4.93)、(41.17±6.10)μg.L-1;tmax为(9.00±5.79)、(9.63±5.33)、(8.05±4.10)h;t1/2为(57.17±10.50)、(56.03±12.86)、(57.6±9.69)h,AUC0-t为(675.85±128.68)、(1 456.80±477.35)、(3 092.66±561.65)μg.h.L-1。美金刚片5 mg多次口服,css-min为(9.80±2.60)μg.L-1,css-max为(21.65±3.58)μg.L-1,tmax为(6.15±3.12)h,t1/2为(48.33±11.60)h。美金刚单次给药,cmax和AUC0-t与剂量有良好的线性相关性(r>0.999);与单次给药相比,多次给药有较强的蓄积效应,蓄积因子R为2.31±0.73;不同性别之间cmax、tmax、AUC0-t、CL、Vd有显著差异(P<0.05),但无临床意义。结论本研究建立的HPLC-MS/MS法简便、快速、专一、灵敏,适用于健康受试者单次及多次口服美金刚片的药动学研究。AIM To study the pharmacokinetics of menatine in healthy volunteers after single-dose and multiple- dose oral administration. METHODS Totally 36 healthy volunteers were divided into three groups, administrated 5 mg, 10 mg and 20 mg of memanatine tablets respectively. The 5 mg group was a multiple-dose group, administrated the dose of memanatine tablets 5 mg q48 h × 7 d. The concentration of memantine in human plasma was measured by HPLC-MS/MS method, and the pharmacokinetics parameters were obtained using BAPP 3.0 software. RESULTS The main pharmacokinetic parameters of single- oral- dose of mematine 5 mg, 10 mg and 20 mg were as follow： cmax （9.32 ± 2.41）, （20.40 ± 4.93）, （41.17 ± 6.10） μg·L-l; tmax （9.00 ± 5.79）, （9.63 ±5.33）, （8.05 ± 4.10） h; t1/2 （57.17 ± 10.50）, （56.03 ± 12.86）, （57.6 ± 9.69） h; AUC0-t （675.85 ± 128.68）, （1 456.80 ± 477.35）, （3 092.66 ± 561.65） μg·h·L-1. The pharmacokineties parameters of multiple-oral-dose of memantine 5 mg were as follows： css-min was （9.80 ± 2.60） μg·L-1, Css-max was （21.65 ± 3.58） μg L-1, tmax was （6.15 ± 3.12） h, t1/2 was （48.33 ± 11.60） h. There was good linear correlation （r 〉 0.999） between cmax or AUC and the close after single oral doses of memantine 5, 10 and 20 mg. Compared with the single- dose, the multiple- dose have the obvious accumulation in vivo with accumulation factor R （2.31 ± 0.73）. There were significant differences between the male and female in cmax, tmax, AUC0-t, CL and Vd （P 〈 0.05）, but with no clinical significance. CONCLUSION The developed HPLC-MS/MS method was convenient, rapid, selective and sensitive, and it was successfully applied to the pharmacokinetics study of single-oral dose and multiple-oral dose of memantine tablets in healthy volunteers.

关 键 词：美金刚 色谱法 高压液相 串联质谱法 投药 口服 药动学 

分 类 号：R969.1[医药卫生—药理学]