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• W4323051374 endingPage "114454" @default.
• W4323051374 startingPage "114454" @default.
• W4323051374 abstract "The organic cation transporter 1 (OCT1) mediates the cell uptake and cytochrome P450 2D6 (CYP2D6) the metabolism of many cationic substrates. Activities of OCT1 and CYP2D6 are affected by enormous genetic variation and frequent drug-drug interactions. Single or combined deficiency of OCT1 and CYP2D6 might result in dramatic differences in systemic exposure, adverse drug reactions, and efficacy. Thus, one should know what drugs are affected to what extent by OCT1, CYP2D6 or both. Here, we compiled all data on CYP2D6 and OCT1 drug substrates. Among 246 CYP2D6 substrates and 132 OCT1 substrates, we identified 31 shared substrates. In OCT1 and CYP2D6 single and double-transfected cells, we studied which, OCT1 or CYP2D6, is more critical for a given drug and whether there are additive, antagonistic or synergistic effects. In general, OCT1 substrates were more hydrophilic than CYP2D6 substrates and smaller in size. Inhibition studies showed unexpectedly pronounced inhibition of substrate depletion by shared OCT1/CYP2D6 inhibitors. In conclusion, there is a distinct overlap in the OCT1/CYP2D6 substrate and inhibitor spectra, so in vivo pharmacokinetics and -dynamics of shared substrates may be significantly affected by frequent OCT1- and CYP2D6-polymorphisms and by comedication with shared inhibitors." @default.
• W4323051374 created "2023-03-04" @default.
• W4323051374 creator A5016938369 @default.
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• W4323051374 date "2023-05-01" @default.
• W4323051374 modified "2023-09-26" @default.
• W4323051374 title "Combined and independent effects of OCT1 and CYP2D6 on the cellular disposition of drugs" @default.
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• W4323051374 doi "https://doi.org/10.1016/j.biopha.2023.114454" @default.
• W4323051374 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36871537" @default.
• W4323051374 hasPublicationYear "2023" @default.
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