Effects of cefoperazone-sulbactam on the pharmacokinetics and pharmacodynamics of warfarin in rats
10.12092/j.issn.1009-2501.2024.11.002
- VernacularTitle:头孢哌酮舒巴坦对胆汁引流大鼠华法林药代动力学和药效动力学的影响
- Author:
Yang CHEN
1
;
Xinyi WANG
;
Boxia LI
;
Zhili WEI
;
Bing SONG
Author Information
1. 兰州大学第一临床医学院,兰州 730000,甘肃
- Publication Type:Journal Article
- Keywords:
warfarin;
pharmacokinetics;
cefoper-azone-sulbactam;
pharmacodynamics;
biliary rain-age
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(11):1212-1219
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To elucidate the effects of cefo-perazone-sulbactam on the pharmacokinetics of warfarin and the mechanism behind the enhance-ment of warfarin's efficacy.METHODS:Thirty-two rats were randomly assigned to four groups:WN(healthy rats after the gastric-administration of 0.125 mg/kg warfarin),WCN(healthy rats after the gastric-administration of 0.125 mg/kg warfarin and 0.3 g/kg cefoperazone-sulbactam),WO(a rat mod-el of biliary drainage after the gastric-administra-tion of 0.125 mg/kg warfarin),WCO(a rat model of biliary drainage after the gastric-administration of 0.125 mg/kg warfarin and 0.3 g/kg cefoperazone-sulbactam).Blood samples were collected at vari-ous time points from the femoral artery to deter-mine the plasma concentration of warfarin and from the tail vein to measure the International Nor-malized Ratio(INR).Warfarin levels were quanti-fied using LC/MS/MS,and pharmacokinetic param-eters were calculated using a non-compartmental model.The expression of P-glycoprotein(P-gp)in the ileal tissues of the WN and WCN groups was determined by Western blotting.RESULTS:Com-pared with the WN group,the WCN group demon-strated a significant increase in AUC0-t,Cmax,and Ka,and a notable decrease in CL/F,and INR values sig-nificantly increased.However,there was no signifi-cant difference in pharmacokinetic parameters and INR values between the WO group and the WCO group.Compared to the WN group,the WO group showed a significant reduction in AUC0-t,Cmax,and CL/F,with an obvious increase in t1/2.The INR of the WCN group was significantly higher than that of the WCO group after 6 hours.Western blotting re-sults indicated a 62.1％reduction in P-gp expres-sion in the ileum of the WCN group compared to the WN group(P＜0.01).CONCLUSION:Cefopera-zone-sulbactam significantly influences the pharma-cokinetic parameters of warfarin and enhances its pharmacological effect by inhibiting intestinal P-gp expression.Biliary drainage significantly affects the pharmacokinetics of warfarin rats,and there is no significant drug interaction between the two after biliary drainage.
