连翘苷对奈玛特韦在大鼠体内药动学的影响  

Effects of phillyrin on the pharmacokinetics of Nirmatrelvir in rats

作　　者：肖鸿丹 杨乐婷 邓海雁 蒋学华[1] 王凌[1] XIAO Hongdan;YANG Leting;DENG Haiyan;JIANG Xuehua;WANG Ling(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;Chengdu Genecore Pharmaceutical Technology Co.,Ltd.,Chengdu,Sichuan,610000 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041 [2]成都臻拓医药科技有限公司,四川成都610000

出　　处：《华西药学杂志》2024年第4期403-406,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的考察连翘苷单次或多次给药对奈玛特韦在大鼠体内药动学特征的影响,为临床联合用药提供参考。方法采用LC-MS/MS法检测大鼠血浆中奈玛特韦的浓度,并验证方法学。将24只SD大鼠随机均分为4组,单次或连续21d经尾静脉注射2mg·kg^(-1)连翘苷,灌胃30mg·kg^(-1)奈玛特韦,考察其药动学特征。采用WinNonlin8.1软件拟合药动学参数。结果单次给药连翘苷后,大鼠体内奈玛特韦的药动学过程无显著变化;连续给药21d连翘苷后,对照组和连翘苷组中奈玛特韦的清除率分别为10.33±1.67、14.77±1.98mL·h^(-1)·g^(-1),AUC_(0-t)分别为2.98±0.56、2.10±0.25h·μg·mL^(-1),AUC_(0-∞)分别为2.99±0.55、2.11±0.25h·μg·mL^(-1);与对照组比较,连翘苷组中奈玛特韦的清除率增加了43.0%,而AUC_(0-t)、AUC_(0-∞)分别降低了42.4%、41.7%。结论长期给予连翘苷会加快奈玛特韦的体内清除,降低生物利用度,提示连翘苷与奈玛特韦联用后可能降低后者的治疗效果,需要谨慎联用。OBJECTIVE To investigate the effects of single or multiple administrations of phillyrin on the pharmacokinetic profile of Nirmatrelvir in rats and to provide a reference for clinical practice.METHODS The concentration of Nirmatrelvir in rat plasma was determined by LC-MS/MS method and the method was subjected to validation.We randomly divided 24 SD rats into 4 groups and administered phillyrin(2 mg kg^(-1),iv)in a single dose or for 21 consecutive days.The pharmacokinetic study was performed with a single dose of Nirmatrelvir(30 mg·kg^(-1),ig).The pharmacokinetic parameters were fitted using WinNonlin 8.1 software.RESULTS There was no significant difference in the pharmacokinetic profile of Nirmatrelvir in rats after a single administration of phllyrin.The clearance rate(CL),AUC_(0-t),and AUC_(0-∞)of nirmatrelvir were 10.33±1.67 mL·h^(-1)·g^(-1),2.98±0.56 h·μg·mL^(-1),2.99±0.55 h-μg·mL^(-1)in the control group,while 14.77±1.98 mL·h^(-1)·g^(-1),2.10±0.25 h·μg.mL^(-1),2.11±0.25 hμg·mL^(-1)in the phillyrin group,after 21 consecutive days of phillyrin administration.The CL was increased by 43.0%,while the AUC_(0-t),and AUC_(0-∞)were decreased by 42.4%and 41.7%,compared with the control group.CONCLUSION The long-term administration of phillyrin accelerated the clearance of Nirmatrelvir and reduced its bioavailability.Combining phillyrin with Nirmatrelvir may diminish the therapeutic efficacy of Nirmatrelvir,which needs to be used with caution.

关 键 词：连翘苷 奈玛特韦 药动学 单次给药 多次给药 药物相互作用 生物利用度 体内 

分 类 号：R917[医药卫生—药物分析学]