title: Prolonged use of aspirin alters human and rat intestinal cells and thereby limits the absorption of clopidogrel.
abstract: Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced responsiveness. The absorption of clopidogrel is regulated by multidrug-resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in intestinal epithelial cells as well, thereby affecting the absorption of clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo, as evidenced by dose-dependent increases in gene, protein, and efflux function. Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption was significantly decreased in the aspirin-treated Caco-2 cells and in rat intestine. Our data provide evidence that prolonged use of aspirin may reduce the intestinal absorption of clopidogrel. Further human studies would be necessary to clarify whether these data have any relevance to prevention of stroke or myocardial infarction.
authors: Department of Neurology, Neuroscience Research Institute, SNUMRC, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors: K-H
authors: KH
authors: Jung
authors: K
authors: K
authors: Chu
authors: S-T
authors: ST
authors: Lee
authors: H-J
authors: HJ
authors: Yoon
authors: J-Y
authors: JY
authors: Chang
authors: W-S
authors: WS
authors: Nam
authors: S-H
authors: SH
authors: Yoon
authors: J-Y
authors: JY
authors: Cho
authors: K-S
authors: KS
authors: Yu
authors: I-J
authors: IJ
authors: Jang
authors: M
authors: M
authors: Kim
authors: S K
authors: SK
authors: Lee
authors: J-K
authors: JK
authors: Roh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin