Effect of ritonavir on bentysrepinine(Y101)pharmacokinetics via P-glycoprotein in vitro and in rats
- VernacularTitle:基于P-gp利托纳韦在体外和大鼠体内对替芬泰药代动力学的影响
- Author:
Yu-feng ZHANG
1
;
Fan-long YANG
;
Yun-hua TENG
;
Yang YUAN
;
Shi-qi DONG
;
Ai-jie ZHANG
;
Hui-rong FAN
Author Information
- Publication Type:Journal Article
- Keywords: drug-drug interaction; bentysrepinine; ritonavir; P-gp; pharmacokinetics; inhibition; induc-tion
- From: Chinese Pharmacological Bulletin 2025;41(10):1859-1866
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.
