罗氟司特及其代谢物在中国健康人群中的群体药代动力学研究  

Population pharmacokinetics of roflumilast and its metabolites in Chinese healthy people

作　　者：过怿赟[1] 李相鸿[1] 梁大虎[1] 孙华[1] 周理想[1] 谢海棠[1] GUO Yi-yun;LI Xiang-hong;LIANG Da-hu;SUN Hua;ZHOU Li-xiang;XIE Hai-tang(Center for Drug Evaluation,Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui Province,China)

机构地区：[1]皖南医学院弋矶山医院药物评价中心,安徽芜湖241001

出　　处：《中国临床药理学杂志》2020年第14期2118-2122,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81173134);皖南医学院中青年科研基金资助项目(WK2015F11)。

摘　　要：目的建立罗氟司特(RFM)和罗氟司特-N-氧化物(RFN)在中国健康人群的群体药代动力学模型,考察影响药代动力学特征的因素。方法23名男性健康志愿者单次口服RFM,检测其血液中RFM和RFN的浓度,用Phoenix NLME 8.1软件构建RFM和RFN的群体药代动力学模型,考察群体药代动力学参数和影响因素。结果在健康志愿者体内,RFM符合双室模型特征,RFN符合单室模型特征。最终模型群体典型值:RFM的滞后时间为0.14 h,中央室分布容积为7508.69 mL,外周室分布容积为2.30×105 mL,吸收速率常数为0.65 h-1,清除率为6661.47 mL·h^-1,室间分布系数(Q)为1.35×104 mL·h^-1;RFN的分布容积为9505.47 mL,清除率为845.24 mL·h^-1。筛选协变量因素,Q-体重指数(Q-BMI)有显著性影响(P<0.001)。结论本研究成功地建立了RFM和RFN在中国健康人群的群体药代动力学模型,最终模型可以有效地估计个体药代动力学参数,筛选协变量因素Q-BMI有显著性影响。Objective To establish a population pharmacokinetic model of roflumilast(RFM)and roflumilast-N-oxide(RFN)in Chinese healthy people,and examine the factors affecting the pharmacokinetic characteristics.Methods Twenty-three healthy male volunteers took a single oral RFM and were blood-tested for the concentrations of RFM and RFN.Phoenix NLME 8.1 software was used to build the population pharmacokinetic models of RFM and RFN and population pharmacokinetic parameters and influencing factors were then investigated.Results In healthy volunteers,RFM conformed to the two-compartment model,and RFN conformed to the single-compartment model.The final model population typical values were as follow:RFM lag time was 0.14 h,the central compartment distribution volume was 7508.69 mL,the peripheral compartment distribution volume was 2.30×10^5 mL,the absorption rate constant was 0.65 h-1,the clearance rate was 6661.47 mL·h^-1 and the inter-compartment distribution coefficient(Q)was 1.35×104 mL·h-1.RFN distribution volume was 9505.47 mL and the clearance rate was 845.24 mL·h^-1.Screened covariate factors Q-body mass index(BMI)exhibited a significant effect(P<0.001).Conclusion This study successfully established a population pharmacokinetic model of RFM and RFN in Chinese healthy people.The final model can effectively estimate individual pharmacokinetic parameters and the screened covariate factors Q-BMI exhibited a significant effect.

关 键 词：罗氟司特 罗氟司特-N-氧化物 健康志愿者 群体药代动力学 

分 类 号：R974[医药卫生—药品]