Effects of phillyrin on the pharmacokinetics of Nirmatrelvir in rats
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 phillyrin.The clearance rate(CL),AUC0-t and AUC0-∞ 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 h·μg·mL-1 in the phillyrin group,after 21 consecutive days of phillyrin administration.The CL was increased by 43.0％,while the AUC0-t and AUC0-∞ 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.
NETL
NSTL
万方数据
