Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents.

ABSTRACT: P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance protein (BCRP) inhibition in vitro and in vivo by P-gp inhibitors derived from natural compounds in previous studies. P-gp inhibitors increased the accumulation of the anticancer drug, topotecan (TPT)-a substrate of P-gp and BCRP, albeit with higher affinity for BCRP-in BCRP-overexpressing cells, resulting in cell death. These dual inhibitors, when orally co-administered with TPT, enhanced TPT bioavailability with slightly reduced total oral clearance (Clt/F) in rats. In xenograft

SUBMITTER: Lee J 

PROVIDER: S-EPMC8071537 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature