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• W2321886230 abstract "Kidney transplanted patients are often treated with immunosuppressive, antihypertensive, and antibiotic drugs such as cyclosporine A (CsA), β-blockers, and fluoroquinolones, respectively. Organic cation transporters (OCT) expressed in the basolateral membrane of proximal tubules represent an important drug excretion route. In this work, the renal expression of OCT after syngeneic and allogeneic kidney transplantation in rats with or without CsA immunosuppression was studied. Moreover, the interactions of CsA, β-blockers (pindolol/atenolol), and fluoroquinolones (ofloxacin/norfloxacin) with rOCT1, rOCT2, hOCT1, and hOCT2 in stably transfected HEK293-cells were studied. Kidney transplantation was associated with reduced expression of rOCT1, while rOCT2 showed only reduced expression after allogeneic transplantation. All drugs interacted subtype- and species-dependently with OCT. However, only atenolol, pindolol, and ofloxacin were transported by hOCT2, the main OCT in human kidneys. While CsA is not an OCT substrate, it exerts a short-term effect on OCT activity, changing their affinity for some substrates. In conclusion, appropriate drug dosing in transplanted patients is difficult partly because OCT are down-regulated and because concomitant CsA treatment may influence the affinity of the transporters. Moreover, drug–drug competition at the transporter can also alter drug excretion rate." @default.
• W2321886230 created "2016-06-24" @default.
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• W2321886230 date "2013-05-03" @default.
• W2321886230 modified "2023-09-30" @default.
• W2321886230 title "Kidney Transplantation Down-Regulates Expression of Organic Cation Transporters, Which Translocate β-Blockers and Fluoroquinolones" @default.
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• W2321886230 doi "https://doi.org/10.1021/mp4000234" @default.
• W2321886230 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23607617" @default.
• W2321886230 hasPublicationYear "2013" @default.
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