脯氨酸恒格列净片在肝功能不全患者中的药物动力学研究  

Pharmacokinetic Study of Proline Henggliflozin Tablets in Patients with Liver Dysfunction

作　　者：杨林 丁莉坤 陈艳 任丹君 高晓华 张娟利 王婧雯 文爱东 Yang Lin;Ding Likun;Chen Yan;Ren Danjun;Gao Xiaohua;Zhang Juanli;Wang Jingwen;Wen Aidong(Department of Pharmacy,First Affiliated Hospital,Air force Medical College,Xi'an 710032,China)

机构地区：[1]空军军医大学第一附属医院药剂科,西安710032

出　　处：《中国药师》2022年第8期1348-1352,共5页China Pharmacist

摘　　要：目的:研究脯氨酸恒格列净片(SHR3824)在健康受试者以及轻、中、重度肝功能不全患者中的药动学(PK)特征,为临床给药方案的制定提供参考。方法:采用多中心、开放、平行、单剂量实验设计,筛选32例受试者,包括肝功能正常的健康受试者和轻、中、重度肝功能不全受试者各8例,空腹口服脯氨酸恒格列净片20 mg后,于给药前和给药后不同时间点采集静脉血,高效液相色谱-串联质谱(LC-MS/MS)法测定受试者血浆中恒格列净浓度,Phoenix WinNonLin 7.0软件统计药动学参数。结果:SHR3824单次给药后,健康受试者,轻度、中度及重度肝功能不全组的C_(max)分别为(324±58.3),(400±83.9),(419±97.8)和(453±71.8)ng·ml^(-1),t_(1/2)分别为(9.70±1.86),(11.5±3.05),(11.6±1.95)和(12.9±2.28)h,AUC_(0-t)分别为(2130±350),(2920±717),(4200±738)和(4290±921)ng·h·ml^(-1),AUC_(0-∞)分别为(2160±349),(2960±729),(4260±748)和(4440±1020)ng·h·ml^(-1),Vd分别为(132±26.6),(116±28.4),(80.6±18.2),(86.6±19.1)L,CL分别为(9.54±1.90),(7.20±2.07),(4.86±1.04),(4.75±1.03)L·h^(-1)。肝功能不全组血浆中恒格列净片的平均暴露水平(C_(max)、AUC_(0-t)和AUC_(0-∞))均显著高于肝功能正常组,差异有统计学意义(P<0.05)。结论:脯氨酸恒格列净片的药动学会受肝功能水平的影响,应根据肝功能调整用药剂量,保证用药安全。Objective:To investigate the pharmacokinetics(PK)of proline henggliflozin tablets(SHR3824)in healthy subjects and patients with mild,moderate and severe liver dysfunction,so as to provide reference for the formulation of clinical administration plan.Methods:A multicenter,open,parallel and single dose experiment was designed and 32 subjects were enrolled,including 8 healthy subjects with normal liver function and 8 subjects with mild,moderate or severe liver dysfunction.After taking 20 mg of proline henggliflozin tablets orally,blood samples were collected at different time points before and after administration,and then analyzed by high performance liquid chromatography tandem mass spectrometry(LC-MS/MS).The parameters of PK were calculated by Phoenix WinNonLin 7.0 software.Results:After a single administration,the Cmax of healthy subjects,mild,moderate and severe liver dysfunction groups was(324±58.3),(400±83.9),(419±97.8)and(453±71.8)ng·ml^(-1),t_(1/2)was(9.70±1.86),(11.5±3.05),(11.6±1.95)and(12.9±2.28)h,AUC_(0-t)was(2130±350),(2920±717),(4200±738)and(4290±921)ng·h·ml^(-1),AUC0-∞was(2160±349),(2960±729),(4260±748)and(4440±1020)ng·h·ml^(-1),Vd was(132±26.6),(116±28.4),(80.6±18.2)and(86.6±19.1)L,and CL was(9.54±1.90),(7.20±2.07),(4.86±1.04)and(4.75±1.03)L·h^(-1),respectively.The average exposure levels of plasma henggliflozin in liver dysfunction groups(C_(max),AUC_(0-t)and AUC_(0-∞))were higher than those in normal liver function group.The results were statistically significant(P<0.05).Conclusion:The pharmacokinetics of proline hengglitazin tablets is affected by liver function,therefore,the dosage of the tablets should be adjusted according to liver function to ensure drug safety.

关 键 词：脯氨酸恒格列净片 药物动力学 肝功能不全患者 剂量调整 

分 类 号：R969.1[医药卫生—药理学]