阿兹夫定联用多替拉韦钠在中国健康受试者中的药代动力学研究  

Pharmacokinetic study of azvudine in combination with dolutegravir in Chinese healthy subjects

作　　者：汪云 吴金伶 马莎莎 李敬[1] 何斌源 万元浩 李雪珂 龙正威 崔桅[1] WANG Yun;WU Jin-ling;MA Sha-sha;LI Jing;HE Bin-yuan;WAN Yuan-hao;LI Xue-ke;LONG Zheng-wei;CUI Wei(PhaseⅠClinical Research Department,Tianjin Union Medical Center,Tianjin 300121,China;Henan Genuine Biotech Co.Ltd,Pingdingshan 467036,Henan Province,China;Shanghai Yugen Medtech Co.Ltd,Shanghai 200131,China)

机构地区：[1]天津市人民医院Ⅰ期临床试验研究室,天津300121 [2]河南真实生物科技有限公司,河南平顶山467036 [3]上海浦济医药科技有限公司,上海200131

出　　处：《中国临床药理学杂志》2023年第13期1938-1942,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价健康受试者同时多次口服阿兹夫定(FNC)和多替拉韦钠(DTG)后,DTG对FNC及FNC对DTG药代动力学的影响。方法本研究采用单中心、随机、开放、三周期、三交叉设计。入组15例受试者,随机分为3组,每组5例,每组受试者随机交叉多次服用FNC/DTG/FNC+DTG。采用液相色谱-串联质谱法(LC-MS/MS)测定血浆中FNC和DTG的浓度。计算主要药代动力学参数并进行统计分析。结果单用DTG和FNC+DTG联用时血浆中DTG的药代动力学参数:C_(max,ss)分别为(4621.33±1248.27)和(4728.67±980.58)ng·mL^(-1),AUC_(0-t,ss)分别为(97530.27±33757.28)和(101136.63±31214.96)ng·h·mL^(-1),AUC_(0-∞,ss)分别为(97477.76±31426.55)和(105485.81±32827.57)ng·h·mL^(-1);单用FNC和FNC+DTG联用时血浆中FNC的药代动力学参数:C_(max,ss)分别为(2.19±0.95)和(3.04±1.37)ng·mL^(-1),AUC_(0-t,ss)分别为(2.72±0.85)和(3.25±1.03)ng·h·mL^(-1),AUC_(0-∞,ss)分别为(3.28±0.76)和(3.37±0.85)ng·h·mL^(-1)。单用DTG和DTG+FNC联用时血浆中DTG的C_(max,ss)、AUC_(0-t,ss)和AUC_(0-∞,ss)几何均数比值分别为103.68%、105.06%和104.38%;单用FNC与DTG+FNC联用时血浆中FNC的C_(max,ss)和AUC_(0-t,ss)几何均数比值分别为137.04%和120.31%。结论FNC对DTG的药代动力学无显著影响,DTG对FNC的药代动力学可能有显著影响。Objective To study the pharmacokinetic interaction between azvudine(FNC)and dolutegravir(DTG)in healthy Chinese subjects.Methods This study was a random,open,three preparations and three-crossover design.15 healthy subjects were enrolled under three sequences:FNC/DTG/FNC+DTG,respectively.Each sequence consisted of 3 cycles,each cycle consisted of 5 consecutive days with an elution period of 7 days.The concentrations of FNC and DTG in plasma were detected by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated and statistically analyzed.Results The main pharmacokinetic parameters of DTG in human treated with DTG alone and combined with FNC were as follows:C_(max,ss)were(4621.33±1248.27)and(4728.67±980.58)ng·mL^(-1),AUC_(0-t,ss)were(97530.27±33757.28)and(101136.63±31214.96)ng·h·mL^(-1),AUC_(0-∞,ss)were(97477.76±31426.55)and(105485.81±32827.57)ng·h·mL^(-1).The main pharmacokinetic parameters of FNC in human treated with FNC alone and combined with DTG were as follows:C_(m ax,ss)were(2.19±0.95)and(3.04±1.37)ng·mL^(-1),AUC_(0-t,ss)were(2.72±0.85)and(3.25±1.03)ng·h·mL^(-1),AUC_(0-∞,ss)were(3.28±0.76)and(3.37±0.85)ng·h·mL^(-1).Compared with the single drug,the 90%confidence intervals of the geometric mean ratios of C_(max,ss),AUC_(0-t,ss)and AUC_(0-∞,ss)of DTG in plasma after combinating with FNC were103.68%,105.06%,104.38%.Compared with the single drug,the 90%confidence intervals of the geometric mean ratios of C_(max,ss),and AUC_(0-t,ss)of FNC in plasma after combinating with DTG were 137.04%and 120.31%.Conclusion FNC had no significant effect on the pharmacokinetics of DTG,but DTG might have significant effect on the pharmacokinetics of FNC,when they were administered jointly to healthy volunteers.

关 键 词：阿兹夫定 多替拉韦 药代动力学 液相色谱-串联质谱法 

分 类 号：R979[医药卫生—药品]