富马酸西他沙星注射液在中国志愿者体内的耐受性与药动学  

Tolerability and pharmacokinetics of sitafloxacin fumarate injection in Chinese volunteers

作　　者：李相鸿[1,3] 辛玉霞 邵静 孙华[1,3] 周理想[1,3] 梁大虎[1,3] 贾元威[1,3] 沈杰[1,3] 谢海棠[1,3] LI Xiang-hong;XIN Yu-xia;SHAO Jing;SUN Hua;ZHOU Li-xiang;LIANG Da-hu;JIA Yuan-wei;SHEN Jie;XIE Hai-tang(Drug Clinical Trial Institution of Yijishan Hospital,Wannan Medical College,Wuhu 241001,China;Nanjing Youke Pharmaceutical Co.,Ltd.,Nanjing 210046,China;Department of Clinical Pharmacy,Wannan Medical College,Wuhu 241002,China)

机构地区：[1]皖南医学院弋矶山医院药物临床试验机构,芜湖241001 [2]南京优科制药有限公司,南京210046 [3]皖南医学院临床药学教研室,芜湖241002

出　　处：《中国新药杂志》2023年第7期712-718,共7页Chinese Journal of New Drugs

基　　金：科技创新团队-“攀峰”计划项目(KPF2019016);皖南医学院中青年科研基金资助项目(WK2012F24)。

摘　　要：目的:评价富马酸西他沙星注射液在中国健康志愿者体内的耐受性和药动学。方法:共入组40例志愿者,男女各20例,分别进行富马酸西他沙星注射液400和500 mg单次给药及300 mg(qd)和400 mg(qd)多次给药研究。试验期间观察药品的不良反应,并监测生命体征、实验室检查等数据的变化,评估药物的耐受性和安全性。采用HPLC-MS/MS法测定西他沙星的血药浓度,计算其主要药动学参数并进行统计学分析。结果:试验期间未发生严重不良事件。多次给药后西他沙星主要药动学参数:300 mg(qd)组多次给药d 1时C_(max),AUC_(0-t),AUC_(0-∞)分别为(2913.00±436.63)μg·L^(-1),(18368.93±4141.28)h·μg·L^(-1)及(19662.17±4820.31)h·μg·L^(-1),d 7时C_(max),AUC_(0-t),AUC_(0-∞)分别为(3080.00±695.11)μg·L^(-1),(22625.89±5729.43)h·μg·L^(-1),(22990.68±5866.94)h·μg·L^(-1);400 mg(qd)组多次给药d 1时C_(max),AUC_(0-t),AUC_(0-∞)分别为(4590.00±894.67)μg·L^(-1),(24113.91±5030.12)h·μg·L^(-1)、(25277.71±5159.69)h·μg·L^(-1),d 7时主要药动学参数C_(max),AUC_(0-t),AUC_(0-∞)分别为(4570.00±1230.04)μg·L^(-1),(30280.20±7007.20)h·μg·L^(-1),(30586.30±7055.85)h·μg·L^(-1)。结论:富马酸西他沙星注射液在中国健康志愿者体内安全耐受。多次给药剂量间呈非线性动力学特征,qd给药体内无明显蓄积,在同一剂量组内主要药动学参数的性别差异无统计学意义。Objective:To evaluate the tolerability and pharmacokinetics of sitafloxacin fumarate injection in healthy Chinese volunteers.Methods:A total of 40 volunteers,half male and half female,were enrolled for single administration and multiple administrations of sitafloxacin fumarate injection.The single dose groups were further divided into 400 mg group and 500 mg group,and the tolerance was investigated.Multiple dose groups were divided into 300 mg(qd)group and 400 mg(qd)group to investigate the tolerability and pharmacokinetics.Adverse reactions were observed during the trial,and changes in vital signs,laboratory tests and other data were monitored to evaluate the safety and tolerability of the drug.The plasma concentrations of sitafloxacin were determined using HPLC-MS/MS,and its pharmacokinetic parameters were calculated and statistically analyzed.Results:No serious adverse events occurred during the trial.Main pharmacokinetic parameters of sitafloxacin after repeated administration are as follows:C_(max),AUC_(0-t),and AUC_(0-∞)are(2913.00±436.63)μg·L^(-1),(18368.93±4141.28)h·μg·L^(-1) and(19662.17±4820.31)h·μg·L^(-1) in 300 mg(qd)group on day 1 of repeated administration;while(3080.00±695.11)μg·L^(-1),(22625.89±5729.43)h·μg·L^(-1),and(22990.68±5866.94)h·μg·L^(-1) on day 7.The corresponding values are(4590.00±894.67)μg·L^(-1),(24113.91±5030.12)h·μg·L^(-1) and(25277.71±5159.69)h·μg·L^(-1) in 400 mg(qd)group on day 1 of repeated administration;while(4570.00±1230.04)μg·L^(-1),(30280.20±7007.20)h·μg·L^(-1) and(30586.30±7055.85)h·μg·L^(-1) on day 7.Conclusion:Sitafloxacin fumarate injection is safe and well tolerated in Chinese healthy volunteers.The dynamic characteristics of multipledoses were nonlinear,without significant accumulation in patients of once-daily administration.There was no statistical significance in gender difference of main pharmacokinetic parameters within the same dose group.

关 键 词：西他沙星 耐受性 药动学 高效液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学] R978[医药卫生—药学]