中国临床药理学杂志2024，Vol.40Issue(15)：2251-2255,5.DOI:10.13699/j.cnki.1001-6821.2024.15.021
JS026及JS026联合JS016注射液在健康受试者中的药代动力学研究
Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
摘要
Abstract
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.关键词
埃特司韦单抗/JS026/JS016/耐受性/安全性/药代动力学Key words
etesevimab/JS026/JS016/tolerability/safety/pharmacokinetics分类
医药卫生引用本文复制引用
田嬿,武晓捷,何金杰,张菁,张文宏,冶会静,王晶晶,李南洋,马娟,谭希,吴钒,王杰,余姝彦..JS026及JS026联合JS016注射液在健康受试者中的药代动力学研究[J].中国临床药理学杂志,2024,40(15):2251-2255,5.基金项目
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）
