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Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug-Drug Interaction in the Gastrointestinal Tract.
Perera, Liyanage Manosika Buddhini; Okazaki, Kenzo; Woo, Yunje; Takahashi, Saori; Zhang, Xieyi; Mizoi, Kenta; Takahashi, Toshinari; Ogihara, Takuo.
Afiliación
  • Perera LMB; Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
  • Okazaki K; Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
  • Woo Y; Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
  • Takahashi S; Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
  • Zhang X; Research Institute for Science and Technology, Tokyo University of Science.
  • Mizoi K; Department of Pharmaceutical Sciences, School of Pharmacy, International University of Health and Welfare.
  • Takahashi T; Medical Affairs Department, Mochida Pharmaceutical Co., Ltd.
  • Ogihara T; Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare.
Biol Pharm Bull ; 47(4): 750-757, 2024.
Article en 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportadoras de Casetes de Unión a ATP / Proteínas de Neoplasias Límite: Humans Idioma: En Revista: Biol Pharm Bull Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transportadoras de Casetes de Unión a ATP / Proteínas de Neoplasias Límite: Humans Idioma: En Revista: Biol Pharm Bull Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Japón