Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug-Drug Interaction in the Gastrointestinal Tract.
Biol Pharm Bull
; 47(4): 750-757, 2024.
Article
in En
| MEDLINE
| ID: mdl-38556260
ABSTRACT
Breast cancer resistance protein (BCRP) is a drug efflux transporter expressed on the epithelial cells of the small intestine and on the lateral membrane of the bile duct in the liver; and is involved in the efflux of substrate drugs into the gastrointestinal lumen and secretion into bile. Recently, the area under the plasma concentration-time curve (AUC) of rosuvastatin (ROS), a BCRP substrate drug, has been reported to be increased by BCRP inhibitors, and BCRP-mediated drug-drug interaction (DDI) has attracted attention. In this study, we performed a ROS uptake study using human colon cancer-derived Caco-2 cells and confirmed that BCRP inhibitors significantly increased the intracellular accumulation of ROS. The correlation between the cell to medium (C/M) ratio of ROS obtained by the in vitro study and the absorption rate constant (ka) ratio obtained by clinical analysis was examined, and a significant positive correlation was observed. Therefore, it is suggested that the in vitro study using Caco-2 cells could be used to quantitatively estimate BCRP-mediated DDI with ROS in the gastrointestinal tract.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
ATP-Binding Cassette Transporters
/
Neoplasm Proteins
Limits:
Humans
Language:
En
Journal:
Biol Pharm Bull
/
Biol. pharm. bull
/
Biological and pharmaceutical bulletin
Journal subject:
BIOQUIMICA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Japan