Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug–Drug Interaction in the Gastrointestinal Tract
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,...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2024/04/01, Vol.47(4), pp.750-757 |
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| container_title | Biological & pharmaceutical bulletin |
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| creator | Perera, Liyanage Manosika Buddhini Okazaki, Kenzo Woo, Yunje Takahashi, Saori Zhang, Xieyi Mizoi, Kenta Takahashi, Toshinari Ogihara, Takuo |
| description | 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. |
| doi_str_mv | 10.1248/bpb.b23-00786 |
| format | Article |
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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.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b23-00786</identifier><identifier>PMID: 38556260</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>absorption rate constant (ka) ; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism ; ATP-Binding Cassette Transporters - metabolism ; Bile ducts ; Breast cancer ; breast cancer resistance protein ; Caco-2 ; Caco-2 Cells ; cell to medium ratio ; Colon cancer ; Colorectal cancer ; Drug interaction ; Drug Interactions ; drug–drug interaction ; Epithelial cells ; Gastrointestinal tract ; Gastrointestinal Tract - metabolism ; Humans ; Neoplasm Proteins - metabolism ; Reactive Oxygen Species - metabolism ; rosuvastatin ; Rosuvastatin Calcium ; Small intestine</subject><ispartof>Biological and Pharmaceutical Bulletin, 2024/04/01, Vol.47(4), pp.750-757</ispartof><rights>2024 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-46745505cd52dc838b88d3d4e00e7c3d1afe6fc1b99863fc5b3386a49060ea023</citedby><cites>FETCH-LOGICAL-c543t-46745505cd52dc838b88d3d4e00e7c3d1afe6fc1b99863fc5b3386a49060ea023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38556260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perera, Liyanage Manosika Buddhini</creatorcontrib><creatorcontrib>Okazaki, Kenzo</creatorcontrib><creatorcontrib>Woo, Yunje</creatorcontrib><creatorcontrib>Takahashi, Saori</creatorcontrib><creatorcontrib>Zhang, Xieyi</creatorcontrib><creatorcontrib>Mizoi, Kenta</creatorcontrib><creatorcontrib>Takahashi, Toshinari</creatorcontrib><creatorcontrib>Ogihara, Takuo</creatorcontrib><title>Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug–Drug Interaction in the Gastrointestinal Tract</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>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. 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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.</description><subject>absorption rate constant (ka)</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Bile ducts</subject><subject>Breast cancer</subject><subject>breast cancer resistance protein</subject><subject>Caco-2</subject><subject>Caco-2 Cells</subject><subject>cell to medium ratio</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Drug interaction</subject><subject>Drug Interactions</subject><subject>drug–drug interaction</subject><subject>Epithelial cells</subject><subject>Gastrointestinal tract</subject><subject>Gastrointestinal Tract - metabolism</subject><subject>Humans</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>rosuvastatin</subject><subject>Rosuvastatin Calcium</subject><subject>Small intestine</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c1O3DAQB3ALFcGW9sgVWeqFS8COP-IcaWgpEgiEaK-WY0_Aq2yy2M6BG-_QN-yT1Nmle-jFc5if_xp7EDqm5IyWXJ236_asLVlBSKXkHlpQxqtClFR8QAtSU1VIKtQh-hjjkmRDSnaADpkSQpaSLNBL0_vBW9Pji8H0r9FHbAaH_YB_-RRG3IwhQG-SHwc8dvhr83Bf3ILzJoHDl2F6-vP2ey74ekgQjN3AfDs9A74yMUf43IjJ53T8OINPaL8zfYTP7_UI_fz-7bH5UdzcXV03FzeFFZylgsuKC0GEdaJ0VjHVKuWY40AIVJY5ajqQnaVtXSvJOitaxpQ0vCaSgMnPPEKn29x1GF-mPIJe-Wih780A4xQ1I2WtaEVklemX_-hynEKeeFaCy7qiimVVbJUNY4wBOr0OfmXCq6ZEz7vQeRc670JvdpH9yXvq1K7A7fS_z8-g2YJlTOYJdsCE5G0PmzheaT4fu9hd1z6boGFgfwFJZJ10</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Perera, Liyanage Manosika Buddhini</creator><creator>Okazaki, Kenzo</creator><creator>Woo, Yunje</creator><creator>Takahashi, Saori</creator><creator>Zhang, Xieyi</creator><creator>Mizoi, Kenta</creator><creator>Takahashi, Toshinari</creator><creator>Ogihara, Takuo</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20240401</creationdate><title>Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug–Drug Interaction in the Gastrointestinal Tract</title><author>Perera, Liyanage Manosika Buddhini ; Okazaki, Kenzo ; Woo, Yunje ; Takahashi, Saori ; Zhang, Xieyi ; Mizoi, Kenta ; Takahashi, Toshinari ; Ogihara, Takuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-46745505cd52dc838b88d3d4e00e7c3d1afe6fc1b99863fc5b3386a49060ea023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>absorption rate constant (ka)</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Bile ducts</topic><topic>Breast cancer</topic><topic>breast cancer resistance protein</topic><topic>Caco-2</topic><topic>Caco-2 Cells</topic><topic>cell to medium ratio</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Drug interaction</topic><topic>Drug Interactions</topic><topic>drug–drug interaction</topic><topic>Epithelial cells</topic><topic>Gastrointestinal tract</topic><topic>Gastrointestinal Tract - metabolism</topic><topic>Humans</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>rosuvastatin</topic><topic>Rosuvastatin Calcium</topic><topic>Small intestine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perera, Liyanage Manosika Buddhini</creatorcontrib><creatorcontrib>Okazaki, Kenzo</creatorcontrib><creatorcontrib>Woo, Yunje</creatorcontrib><creatorcontrib>Takahashi, Saori</creatorcontrib><creatorcontrib>Zhang, Xieyi</creatorcontrib><creatorcontrib>Mizoi, Kenta</creatorcontrib><creatorcontrib>Takahashi, Toshinari</creatorcontrib><creatorcontrib>Ogihara, Takuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perera, Liyanage Manosika Buddhini</au><au>Okazaki, Kenzo</au><au>Woo, Yunje</au><au>Takahashi, Saori</au><au>Zhang, Xieyi</au><au>Mizoi, Kenta</au><au>Takahashi, Toshinari</au><au>Ogihara, Takuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug–Drug Interaction in the Gastrointestinal Tract</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>47</volume><issue>4</issue><spage>750</spage><epage>757</epage><pages>750-757</pages><artnum>b23-00786</artnum><issn>0918-6158</issn><eissn>1347-5215</eissn><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. 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| subjects | absorption rate constant (ka) ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism ATP-Binding Cassette Transporters - metabolism Bile ducts Breast cancer breast cancer resistance protein Caco-2 Caco-2 Cells cell to medium ratio Colon cancer Colorectal cancer Drug interaction Drug Interactions drug–drug interaction Epithelial cells Gastrointestinal tract Gastrointestinal Tract - metabolism Humans Neoplasm Proteins - metabolism Reactive Oxygen Species - metabolism rosuvastatin Rosuvastatin Calcium Small intestine |
| title | Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug–Drug Interaction in the Gastrointestinal Tract |
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