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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

  • 摘要: 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。

     

    Abstract: 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 rasagiline 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;AUC0-8 h (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.

     

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