中国临床药理学杂志2024，Vol.40Issue(14)：2108-2112,5.DOI:10.13699/j.cnki.1001-6821.2024.14.022
注射用伏立康唑在中国健康受试者中的生物等效性研究
Bioequivalence study of voriconazole injection in Chinese healthy subjects
摘要
Abstract
Objective To evaluate the bioequivalence and safety of two voriconazole for injection in healthy Chinese subjects,and to explore the safety of the excipient sulfobutyl-β-cyclodextrin.Methods A single-center,single-dose,randomized,open-label,two-preparation,two-period,double-crossover trial design.A total of 18 healthy subjects were enrolled and administrated with a single intravenous infusion of voriconazole test drug and reference drug at 4 mg·kg-1 under fasting conditions,with a sequence determined by randomization.The concentrations of voriconazole in plasma and sulfobutyl-β-cyclodextrin in urine were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters of voriconazole in plasma,and SAS(version 9.4)software was used to calculate pharmacokinetic parameters of sulfobutyl-β-cyclodextrin in urine and bioequivalence analysis.Results Major pharmacokinetic parameters of voriconazole in plasma after a single intravenous infusion of voriconazole test drug and reference drug in 18 healthy subjects in a fasted state were as follows:Cmax were(2 177.00±399.10)and(2 265.00±378.70)ng·mL-1;AUC0-t were(14 612.07±8 182.95)and(15 144.69±7 814.02)ng·h·mL-1;AUC0-∞ were(16 217.48±10 862.78)and(16 863.18±10695.75)ng·h·mL-1;tmax were 2.00 and 1.98 h,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the two drugs were within the equivalence range of 80.00％to 125.00％.Conclusion The two voriconazole for injection preparations were bioequivalent and safe when administered by intravenous infusion under fasting conditions in healthy Chinese subjects.关键词
注射用伏立康唑/磺丁基-β-环糊精/生物等效性/药代动力学/安全性Key words
voriconazole for injection/sulfobutyl-β-cyclodextrin/pharmacokinetics/bioequivalence/safety分类
医药卫生引用本文复制引用
严新,杨双,阳晓燕,姚安,崔畅,阳国平,黄洁..注射用伏立康唑在中国健康受试者中的生物等效性研究[J].中国临床药理学杂志,2024,40(14):2108-2112,5.基金项目
湖南省自然科学基金资助项目(2020JJ5852) （2020JJ5852）
