甲磺酸雷沙吉兰片的生物等效性研究及非酪胺控制饮食条件下对中国健康受试者血压的影响

Bioequivalence Study of Rasagiline Mesylate Tablets and Effect of Tyramine-Uncontrolled Diet on Blood Pressure in Chinese Healthy Volunteers

目的初步比较2种甲磺酸雷沙吉兰片在中国健康受试者中的生物等效性,并探讨不控制酪胺摄入的情况下服用甲磺酸雷沙吉兰片对中国健康受试者血压的影响。方法在24名中国健康受试者中进行随机、开放、两制剂、单剂量、两周期、两序列、双交叉空腹和餐后状态下的生物等效性预试验;同步采集血样、监测血压,获取药代动力学参数,评估药物安全性,尤其是对血压的影响。结果受试者服用受试制剂和参比制剂后,空腹组达峰浓度(C_(max))为(8389.09±4159.42)pg/mL、(8325.00±3978.49)pg/mL;0-t时血药浓度时间曲线下面积(AUC_(0-t))为(5071.98±1610.79)h•pg/mL、(5080.93±2117.82)h•pg/mL;0-∞时血药浓度时间曲线下面积(AUC_(0-∞))为(5149.05±1640.41)h•pg/mL、(5191.22±2149.20)h•pg/mL;餐后组C_(max)为(3258.08±1213.33)pg/mL、(2500.00±730.73)pg/mL;AUC_(0-t)为(5630.80±1817.24)h•pg/mL、(4659.80±1072.91)h•pg/mL;AUC_(0-∞)为(5488.83±1714.69)h•pg/mL、(4697.23±1113.66)h•pg/mL。空腹状态下受试制剂和参比制剂的C_(max),AUC_(0-t),AUC_(0-∞)经对数转换后90%置信区间分别为73.13%~138.23%、90.73%~119.50%、89.99%~118.70%;餐后状态下分别为96.96%~162.15%、102.90%~133.59%、102.41%~135.37%。结论受试制剂和参比制剂在药代动力学和安全性方面具有可比性,进食会影响药物的系统暴露和达峰时间;不控制酪胺摄入的情况下对空腹组与餐后组收缩压和舒张压的影响无显著差异。

Objective To preliminarily compare the bioequivalence of two types of Rasagiline Mesylate Tablets in Chinese healthy volunteers,and to investigate the effect of tyramine-uncontrolled diet on blood pressure in Chinese healthy volunteers.Methods A randomized,open-label,two formulations,single-dose,two cycles,two sequences,and double cross-over fasting/postprandial bioequivalence trial was conducted in 24 Chinese healthy volunteers.Meanwhile,the blood samples were collected,blood pressure was monitored,pharmacokinetic parameters were calculated,and the drug safety was evaluated,especially the effect of drugs on blood pressure.Results In the fasting group,after taking the test formulation and reference formulation,the peak concentrations(C_(max))were(8389.09±4159.42)pg/mL and(8325.00±3978.49)pg/mL,respectively;the areas under the curve at 0-t(AUC_(0-t))were(5071.98±1610.79)h•pg/mL and(5080.93±2117.82)h•pg/mL,respectively;the areas under the curve at 0-∞(AUC_(0-∞))were(5149.05±1640.41)h•pg/mL and(5191.22±2149.20)h•pg/mL,respectively.In the postprandial group,after taking the test formulation and reference formulation,the C_(max) were(3258.08±1213.33)pg/mL and(2500.00±730.73)pg/mL,respectively;the AUC_(0-t) were(5630.80±1817.24)h•pg/mL and(4659.80±1072.91)h•pg/mL,respectively;the AUC_(0-∞)were(5488.83±1714.69)h•pg/mL and(4697.23±1113.66)h•pg/mL,respectively.The 90%confidential intervals(CI)of the logarithmic transformation of C_(max),AUC_(0-t) and AUC_(0-∞)for the test formulation and reference formulation in the fasting state were in the range of 73.13%-138.23%,90.73%-119.50%and 89.99%-118.70%,respectively;and those in the postprandial state were in the range of 96.96%-162.15%,102.90%-133.59%,and 102.41%-135.37%,respectively.Conclusion Pharmacokinetics and safety of the test formulation and reference formulation were comparable and food could affect the systemic exposure and peak performance.There was no significant difference in the effect of tyramine-uncontrolled diet on systolic and diastolic blood pressure between the fasting group and postprandial group.