中国临床药理学杂志2025，Vol.41Issue(3)：387-392,6.DOI:10.13699/j.cnki.1001-6821.2025.03.018
德拉沙星在中国健康受试者中药代动力学/药效学研究
Pharmacokinetics/pharmacodynamic study of delafloxacin in Chinese healthy subjects
摘要
Abstract
Objective To evaluate the pharmacokinetic characteristics and safety of delafloxacin,a new fluoroquinolone drug,in Chinese healthy subjects,and to evaluate the expected microbiological efficacy of delafloxacin in treating infections caused by Staphylococcus aureus and Streptococcus pneumoniae through pharmacokinetic/pharmacodynamic analysis.Methods This trial consists of two parts.The first part is a randomized,double-blind,placebo-controlled,single-dose/multiple-dose administration trial with a dose range of 150-450 mg.The second part is a randomized,open-label,double-period,self-crossover trial comparing the pharmacokinetic similarities between a 300 mg intravenous infusion of the test drug and the reference drug.Combined with the in vitro pharmacodynamic data of delafloxacin against Staphylococcus aureus and Streptococcus pneumoniae clinically isolated in China,the Monte Carlo simulation method was used to analyze the probability of target attainment and cumulative fraction of response of the 300 mg q12 h intravenous infusion over 60 min and to evaluate the expected microbiological efficacy.Results After administering 150,300 and 450 mg of delafloxacin to Chinese healthy subjects in single doses,the Cmax,AUC0-t and AUC0-∞ increase proportionally with the dose.The apparent volume of distribution ranged from 45.79 to 144.38 L.The elimination half-life of each dose group ranged from 2.99 to 11.87 h.The cumulative urinary excretion rates of(47.69±8.11)％and(73.71±9.32)％were observed for single doses of 300 and 450 mg,respectively,suggesting that the primary route of excretion was renal.The 90％confidence interval of Cmax,AUC0-tand AUC0-∞ of test drug over reference drug after single-dose intravenous infusion are all within 80.00％-125.00％.After reaching steady state with multiple-dose administration in the 300 mg group,the plasma exposure level was similar to that of the single-dose administration group.Conclusion Single-dose intravenous infusion of 150-450 mg delafloxacin in healthy subjects showed linear pharmacokinetic characteristics,and there was no accumulation after 300 mg q12 h administration.Adverse effects were mild,indicating good safety,and good microbiological efficacy.关键词
德拉沙星/抗菌药物/药代动力学/药效学/安全性Key words
delafloxacin/antibacterial drug/pharmacokinetics/pharmacodynamics/safety分类
医药卫生引用本文复制引用
朱旭,卢春林,宣景安,卞星晨,郁继诚,王晶晶,杨海静,曹国英,武晓捷,张菁,陈昱竹..德拉沙星在中国健康受试者中药代动力学/药效学研究[J].中国临床药理学杂志,2025,41(3):387-392,6.基金项目
国家自然科学基金面上基金资助项目(82173896) （82173896）
上海申康医院发展中心研究型医师创新转化能力培训基金资助项目(SHDC2022CRS004B) （SHDC2022CRS004B）
