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目的研究健康中国男性志愿者口服10mg盐酸美金刚胶囊和片剂后的药代动力学和生物等效性。方法本实验研究采用单剂量、随机、开放、双周期的方法,在中国健康男性志愿者中进行研究。志愿者分别服用10mg单剂量的受试制剂或参比制剂,经过1周的清洗期后,再服药另一种药物。经过12小时禁食后,服用研究药物,在360h内的各个时间点分别抽取血样。药物的血药浓度用液质串联色谱(LC/MS)法测定。两种制剂的药动学参数Cmax,tmax,t1/2,AUC0-t,AUC0-∞可由血浆药物浓度计算而来。经过对数转换后Cmax,AUC0-t和AUC0-∞的可信区间在80%～125%之间时,认为两制剂生物等效。安全性评价用监测生命体征,实验室检查(血常规,血液生化,肝功和尿常规),和询问受试者的方法来评价。结果20名中国男性志愿者经过筛选后入选(平均值[标准差]:年龄为22.40[1.96]岁,体重为70.90[4.34]kg,身高为177.45[5.66]cm),并全部完成试验。美金刚受试制剂和参比制剂的主要药动学参数分别如下所示:Cmax(12.9[3.2],12.2[3.8])ng·mL-1;tmax(6.1[2.4],6.6[2.6])h;AUC0-t(902.4[291.6],845.1[255.7])ng·mL-1.h;AUC0-∞(977.0[328.7],932.7[261.6])ng·mL-1.h;t1/2(63.0[14.4],63.8[12.3])h。经过对数转换后Cmax,AUC0-t和AUC0-∞的90%置信区间分别为97.5～118.1,94.9～118.7和92.2～115.1。试验中无不良反应发生。结论在这个中国男性志愿者的小样本研究中,受试者单剂量口服10mg的美金刚胶囊(受试制剂)和美金刚片(参比制剂)具有生物等效性,并具有良好的耐受性。
Objective To study the pharmacokinetics and bioequivalence of 10 mg memantine hydrochloride capsules and tablets in healthy Chinese male volunteers. Methods This experiment was conducted in a single dose, randomized, open and double cycle method in healthy Chinese male volunteers. The volunteers took a single dose of 10 mg of the test formulation or the reference formulation, respectively, and after a one-week washout period, they took another drug. After 12 hours of fasting, taking the study drug, blood samples were taken at various time points within 360 hours. Drug plasma concentration by liquid chromatography tandem chromatography (LC / MS) method. The pharmacokinetic parameters Cmax, tmax, t1 / 2, AUC0-t and AUC0-∞ of the two preparations can be calculated from the plasma drug concentration. Two formulations were considered bioequivalent when the confidence intervals for Cmax, AUC0-t and AUC0-∞ were between 80% and 125% after logarithmic conversion. Safety assessments are evaluated by monitoring vital signs, laboratory tests (blood tests, blood biochemistry, liver function and urinalysis), and methods of interrogating subjects. Results Twenty Chinese male volunteers were screened (mean [SD]: age 22.40 [1.96] years old, weighing 70.90 [4.34] kg and height 177.45 [5.66] cm) and completed the experiment. The main pharmacokinetic parameters of the memantine test and reference preparations are as follows: Cmax (12.9 [3.2], 12.2 [3.8]) ng · mL-1; tmax (6.1 [2.4], 6.6 [2.6]) h; AUC0-t (902.4 [291.6], 845.1 [255.7]) ng · mL-1.h; AUC0-∞ (977.0 [328.7], 932.7 [261.6]) ng · mL- 63.0 [14.4], 63.8 [12.3]) h. The 90% confidence intervals of Cmax, AUC0-t and AUC0-∞ after logarithmic transformation are 97.5-118.1, 94.9-118.7 and 92.2-115.1, respectively. No adverse reactions in the test occurred. Conclusions In a small sample study of Chinese male volunteers, subjects were given a single dose of 10 mg memantine (test formulation) and memantine (reference formulation) as bioequivalent and well tolerated .