盐酸美金刚片在健康人体内的药动学研究

Pharmacokinetic Study of Memantine Hydrochloride Tablet in Healthy Volunteers

目的:研究单次给予盐酸美金刚片在健康人体内的药动学。方法:选取20名健康受试者,分别单次口服低(10 mg)、高(20 mg)剂量组的盐酸美金刚片后采用液-质联用法进行血药浓度测定。色谱柱为Hedera ODS-C18,流动相为20 mmol/L醋酸铵水溶液(含0.05%的甲酸)-甲醇(47∶53),流速为0.45 ml/min,柱温为38℃,进样量为5μl。选择性离子检测(SIM),检测对象为美金刚,[M+H]+离子,m/z 180.2;内标(多奈哌齐),[M+H]+离子,m/z 380.3。结果:单次口服盐酸美金刚片10 mg和20 mg后,主要药动学参数分别为cmax(13.64±3.12)、(29.18±5.97)ng/ml,tmax(7.8±2.6)、(8.0±4.6)h,t1/2(60.5±7.3)、(67.1±9.4)h,AUC0-288 h(1 110.4±353.2)、(2 605.5±432.1)ng·h/ml。结论:低、高剂量组消除半衰期及达峰时间相近,AUC0-288 h、cmax均与剂量基本呈正比递增关系,无性别差异。

OBJECTIVE： To study the blood concentration and pharmacokinetic parameters of single dose of Memantine hydro- chloride tablets in healthy volunteers. METHODS： 20 healthy subjects were selected and given low-dose （10 mg） and high-dose （20 mg） Memantine hydrochloride tablets, respectively. LC-MS method was adopted to determine the blood concentration of drugs. The determination was performed on Hedera ODS-C18 column with mobile phase consisted of 20 mmol/L ammonium acetate （con- raining 0.05% formic acid）-methanol （47：53） at the flow rate of 0.45 ml/min. The column temperature was 38 ℃, and sample size was 5 μl. MS detection condition was as follows： selective ion measurement （SIM）, memantine as detection object, [M＋H] ion, m/z 180.2; donepezil as internal standard, [M＋H] ion, m/z 380.3. RESULTS： After single oral dose of Memantine hydrochloride tablets （10 mg and 20 mg）, main pharmacokinetic parameters were as follows： Cmax was （13.64±3.12） ng/ml and （29.18 ±5.97） ng/ml; tmax was （7.8 ± 2.6） h and （8.0± 4.6） h; t1/2 was （60.5± 7.3）h and （67.1 ± 9.4）h; AUC8-288b was （1 110.4± 353.2） ng.lgml and （2 605.5 ± 432.1） ng-h/ml. CONCLUSIONS： The elimination half life and peak time of low-dose group are close to those of high-dose group. The dose increases progressively with AUC0-288 h, cmax proportionally. There is no gender difference.