高脂餐对健康受试者口服复达那非片药代动力学的影响  

Effect of high-fat meal on the pharmacokinetics of fadanafil tablet in healthy Chinese volunteers

作　　者：刘娜[1] 牛晓也 高玉玲 黄杨 袁秀玲 齐春梅 王毅韬 李海燕 LIU Na;NIU Xiao-ye;GAO Yu-ling;HUANG Yang;YUAN Xiu-ling;QI Chun-mei;WANG Yi-tao;LI Hai-yan(Clinical Research Center of ZGC Science Town,Beijing Haidian Hospital,Haidian Section of Peking University Third Hospital,Beijing 100080,China;Drug Clinical Trial Center,Peking University Third Hospital,Beijing 100191,China;Xuanzhu Biopharmaceutical Ltd,Beijing 100025,China)

机构地区：[1]北京市海淀医院、北京大学第三医院海淀院区中关村科学城临床研究中心,北京100080 [2]北京大学第三医院药物临床试验机构,北京100191 [3]轩竹医药科技有限公司,北京100025

出　　处：《中国临床药理学杂志》2020年第20期3345-3349,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的此研究为单中心、随机、开放、双周期交叉研究,旨在评价高脂餐对健康受试者单次口服复达那非片药代动力学(PK)的影响及安全性。方法14例合格的健康男性受试者,按1∶1随机分成A、B组,每组各7例受试者。试验分成2个周期,中间洗脱7 d。第1周期:A组受试者于第1天进行空腹给药,B组受试者于第1天进行高脂餐后给药(高热量,总热量945千卡,高脂,占总热量的51%,早餐后30 min口服试验药物)。第2周期:A组受试者于第8天进行高脂餐后给药,B组受试者于第8天进行空腹给药。两周期均采用单次口服给药,给药剂量均为100 mg。受试者在每一周期给药前(给药前30 min内)和给药后0.25,0.5,0.75,1,1.5,2,2.5,4,6,8,12和24 h进行PK血样的采集。结果入组的14例健康男性受试者均完成研究并进行了PK分析。血浆中XZP-5849的Cmax、AUC0-t和AUC0-∞的几何均值比值(高脂餐/空腹)分别为99.08%,125.78%和120.81%,其比值的90%CI分别为82.69%~118.72%,112.30%~140.89%和108.66%~134.33%;与空腹相比,高脂餐后血浆中复达那非的原型药物(XZP-5849)的峰浓度(Cmax)基本一致,从零时刻到末次可测浓度时刻的血药浓度-时间曲线下面积(AUC0-t)和从零时刻到推算的无穷时间的血药浓度-时间曲线下面积(AUC0-∞)分别增加了25.78%和20.81%,达峰时间(Tmax)中位值延迟了2.24 h。血浆中复达那非代谢产物(XZP-3822)的Cmax、AUC0-t和AUC0-∞的几何均值比值(高脂餐/空腹)分别为76.46%,105.29%和106.04%,其比值的90%CI分别为63.45%~92.14%,93.09%~119.10%和94.63%~118.82%,与空腹相比,高脂餐后血浆中XZP-3822的Cmax下降了23.54%,AUC0-t和AUC0-∞基本一致,Tmax中位值延迟了1.99 h。本研究未发生严重不良事件(SAE),无受试者因不良事件退出研究,治疗后发生的不良事件(AE)均为不良事件通用术语评价标准(CTCAE)1级,未采取任何治疗措施而痊愈。结论高脂餐饮食对健康男性受试者单次口服复达�Objective A single-center,randomized,open,2-period crossover study was performed to evaluate the effect of high-fat food on the pharmacokinetics of single oral dose of Fadanafil(XZP-5849)tablet and its safety.Methods Forteen eligible healthy male subjects were randomized in 1∶1 ratio to A and B groups to receive investigational product in a 2-period(7 days washout between the 2 periods)crossover fashion.In period 1 on Day 1,subjects in group A received investigational products in fasted condition while subjects in group B received investigational products in fed(high-fat food)condition(had a high-fat breakfast with 945 kCal,51%of which were fat,30 min before dosing).In period 2 on day 8,subjects in group A received investigational products in fed condition,while subjects in group B received investigational products in fasted condition.In both periods,a single oral dose of XZP-5849 tablet(100 mg)were administered.Blood samples were drawn at pre-dose(30 minutes pre-dose),0.25,0.5,0.75,1,1.5,2,2.5,4,6,8,12 and 24 hours post-dose.Results All the enrolled 14 healthy male subjects completed the study with PK analyzed.Geometric mean ratios(fed breakfast/fasted)of XZP-5849 for maximum plasma concentration(Cmax),the area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration(AUC0-t)and the area under the plasma concentration-time curve from time 0 extrapolated to infinity(AUC0-∞)were 99.08%(90% confidence interval 82.69%-118.72%),125.78%(90% confidence interval 112.30%-140.89%)and 120.81%(90% confidence interval 108.66%-134.33%),respectively.There was no food impact on the Cmax of XZP-5849.AUC0-t and AUC0-∞of XZP-5849 in the fed condition increased by 25.78% and 20.81%,respectively.The median time to maximum plasma concentration(Tmax)in the fed condition delayed 2.24 h,compared to the fasted group.Geometric mean ratios(fed breakfast/fasted)of XZP-3822,a metabolite of XZP-5849,Cmax,AUC0-t and AUC0-∞were 76.46%(90% confidence interval 63.45%-92.14%),105.29%(90% confide

关 键 词：复达那非片 高脂餐 健康受试者 磷酸二酯酶-5抑制剂 

分 类 号：R97[医药卫生—药品]