高脂餐对中国健康受试者口服DDO-3055片药动学和药效学的影响  

Effect of high fat meal on pharmacokinetics and pharmacodynamics of DDO-3055 tablets in healthy Chinese volunteers

作　　者：许莉 田蕾 李子煦 崔文 贾友宏 高宇雄 胡彬 XU Li;TIAN Lei;LI Zi-xu;CUI Wen;JIA You-hong;GAO Yu-xiong;HU Bin(National Clinical Research Center for Cardiovascular Diseases,Phase I Ward,NHC Key Laboratory of Clinical Research for Cardiovascular Medications,Fuwai Hospital,Chinese Academy of Medical Sciences,National Center for Cardiovascular Diseases,Beijing 100037,China;Jiangsu Hengrui Medicine Co.,Ltd.,Lianyungang 222047,China)

机构地区：[1]中国医学科学院阜外医院国家心血管病中心国家心血管疾病临床医学研究中心Ⅰ期病房国家卫生健康委员会心血管药物临床研究重点实验室,北京100037 [2]江苏恒瑞医药股份有限公司,连云港222047

出　　处：《中国新药杂志》2022年第12期1183-1187,共5页Chinese Journal of New Drugs

摘　　要：目的:评价高脂餐对中国健康受试者单次口服DDO-3055片药动学(PK)和药效学(PD)的影响。方法:采用随机、开放、两阶段双交叉试验设计。筛选合格的健康男性受试者14例,随机分成A,B两组,每组各7例受试者。试验分成2个阶段,第1阶段:A组受试者于d 1高脂餐后给药,B组受试者于d 1空腹给药。第2阶段:A组受试者于d 7空腹给药,B组受试者于d 7高脂餐后给药。两阶段均采用单次口服给药,给药剂量均为200 mg。受试者在每一阶段给药前60 min内和给药后0.5,1,1.5,2,2.5,3,4,6,8,12,24和48 h进行PK血样采集,在每一阶段给药前60 min内和给药后4,8,12,24和48 h进行PD血样采集。结果:入组的14例健康男性受试者均完成本研究。血浆中DDO-3055的峰浓度(C_(max)),0-t时间的血药浓度时间曲线下面积(AUC_(0-t)),AUC_(0-∞)的几何均值比(高脂餐/空腹)分别为77.9%,95.0%,95.0%,其比值的90%CI分别为67.6%~89.7%,85.9~105%,85.9%~105%。与空腹相比,高脂餐后血浆DDO-3055的C_(max)降低22.1%,AUC_(0-t)和AUC_(0-∞)均降低5.0%。与空腹给药相比,高脂餐后血清平均内源性促红素(EPO)最大值与空腹给药相比略有增加,分别为15.015和14.739 mIU·mL^(-1);餐后平均EPO最大值较基线变化百分比与空腹给药相比有所增加,分别为92.976%和72.796%。本研究未发生不良事件、严重不良事件。结论:高脂餐饮食对健康男性受试者单次口服DDO-3055片的AUC_(0-t)和AUC_(0-∞)无影响,C_(max)降低,说明食物对DDO-3055片的吸收速度有一定影响,但影响较弱。Objective:To evaluate the effect of high fat diet on the pharmacokinetics and pharmacodynamics of single oral dose of DDO-3055 tablets in Chinese healthy volunteers.Methods:A randomized,open,two-period,cross-over trial was conducted.Fourteen eligible healthy male volunteers were selected and randomly divided into two groups:Group A and Group B,with 7 volunteers in each group.The experiment was divided into two periods.Period 1:Group A was given the drug under fed(high fat food)condition on the first day,and Group B was given the drug under fasted condition on the first day.Period 2:Group A was given the drug under fasted condition on the 7th day,and Group B was given the drug under fed condition on the 7th day.In both periods,a single oral dose of DDO-3055(200 mg)was administered.PK blood samples were drawn at pre-dose(60 min pre-dose),0.5,1,1.5,2,2.5,3,4,6,8,12,24 and 48 h post-dose.PD blood samples were drawn at pre-dose(60 min predose)4,8,12,24 and 48 h post-dose.Results:All the enrolled 14 healthy male volunteers completed the study with the PK and PD analyzed.Geometric mean ratios(high fat fed/fasted)of plasma DDO-3055 for C_(max),AUC_(0-t) and AUC_(0-∞)were 77.9%(90%CI 67.6%~89.7%),95.0%(90%CI 85.9%~105%)and 95.0%(90%confidence interval 85.9%~105%),respectively.C_(max),AUC_(0-t) and AUC_(0-∞)of plasma DDO-3055 in fed condition decreased by 22.1%,5.0%and 5.0%,respectively.The mean endogenous erythropoietin(EPO)level in fed condition was 15.015 mIU·mL^(-1),increased slightly compared to the 14.739 mIU·mL^(-1)in fasted condition.The maximal percentage change of EPO from baseline in fed condition was 92.976%,increased compared to the 72.796%in fasted condition.No adverse events or serious adverse events occurred in this study.Conclusion:High fat food had no effect on AUC_(0-t) and AUC_(0-∞)of single dose of DDO-3055 tablets at 200 mg,but decreased C_(max)slightly,indicating that food has certain but weak effect on the absorption rate of DDO-3055 tablets.

关 键 词：DDO-3055片 药动学 药效学 高脂餐 健康受试者 

分 类 号：R969.1[医药卫生—药理学]