饮食对甲磺酸雷沙吉兰人体药代动力学的影响

Food effects on the human pharmacokinetics of rasagiline mesylate

采用开放、随机、自身对照交叉试验设计,考察高脂餐对雷沙吉兰在健康中国人体内的药代动力学影响。12名健康受试者分别于空腹或高脂餐后,单次口服甲磺酸雷沙吉兰片1 mg,0～8 h间隔采集血样,0～24 h间隔采集尿样,采用LC-MS/MS法测定雷沙吉兰的血药与尿药浓度,DAS 2.1计算药代动力学参数。雷沙吉兰在0.006 4～12.8 ng/mL范围内线性关系良好。测得空腹和高脂餐后口服甲磺酸雷沙吉兰片1 mg,雷沙吉兰的cmax分别为(3.93±1.55)和(1.58±0.75)ng/mL,tmax分别为(0.5±0.2)和(0.9±0.8)h,t1/2分别为(1.08±0.78)和(1.51±0.63)h,AUC0-8 h分别为(2.81±0.92)和(2.43±0.77)ng.h/mL,24 h内以雷沙吉兰形式经尿液分别排泄(0.20±0.12)%和(0.20±0.09)%。结果表明建立的LC-MS/MS法准确可靠,高脂饮食对雷沙吉兰的吸收速率有显著影响,但对吸收程度、尿排泄率无显著影响。

To evaluate the effects of high-fat diet on the pharmacokinetic profile of rasagiline in healthy Chinese volunteers, an open-label, randomized, crossover study was conducted. 12 Healthy Chinese volunteers were given a single oral dose of 1 mg rasagiline mesylate tablets after an over-night fast or after a high-fat breakfast. The rasagi- line concentrations in plasma and urine were determined by validated LC-MS/MS methods. The pharmacokinetic parameters were estimated by DAS 2. 1 software. The calibration curves of rasagiline in both plasma and urine were linear over the range of 0. 006 4 to 12. 8 ng/mL. The main pharmacokinetic parameters of rasagiline under fast and high fat postprandial were as follows： Cmax（3. 93 --±1. 55） and （ 1.58 ±0. 75） ng/mL;tmax（0. 5 ±0.2） and （0. 9 ±0. 8） h; t1/2（1.08 ±0. 78） and （1.51 ±0. 63） h; AUC0-8h（2.81±0. 92） and （2.43 ±0.77） ng·h/mL, respectively, with the urine excretion of the unchanged form within 24 h as （ 0. 20 ±0. 12） % and （ 0.20 ± 0.09） % of the oral dose of rasagiline. The results showed that high fat postprandial has obvious effects on the absorption rate of rasagiline, but no effect on the absorption amount and cumulative excretion.