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• W2892397910 abstract "ATP-binding cassette, subfamily B, member 1 (ABCB1) transport, or P-glycoprotein (P-gp), is a transport protein that is involved in the absorption and the efflux of some antidepressants, such as selective serotonin reuptake inhibitors. The purpose of the current research was to assess the influence of the ABCB1 1199G>A polymorphism on P-gp-mediated efflux ability toward escitalopram, citalopram, paroxetine, fluoxetine, and sertraline. Two recombinant LLC-PK1 cell systems transfected with ABCB1 1199G and 1199A alleles were constructed. The effects of the 1199G>A polymorphism on P-gp efflux activity toward escitalopram, citalopram, paroxetine, fluoxetine, and sertraline were observed by cytotoxicity, intracellular accumulation, and kinetic tests. The LLC-PK1 cells overexpressing the ABCB1 carrying 1199A allele showed higher resistance to escitalopram (1.92-fold), citalopram (1.68-fold), paroxetine (2.41-fold), and sertraline (1.92-fold) than cells transfected with the 1199G allele (p < 0.01), whereas the two types of recombinant cells displayed a comparable sensitivity to fluoxetine (p > 0.05). The intracellular contents of escitalopram (2.86-fold), citalopram (2.59-fold), paroxetine (2.43-fold), and sertraline (2.36-fold) in cell lines transfected with the 1199A allele were lower than cells overexpressing the 1199G allele (p < 0.01). Moreover, the net efflux ratios of P-gp-mediated escitalopram (2.61-fold), citalopram (2.50-fold), paroxetine (3.17-fold), and sertraline (4.29-fold) in cells overexpressing the 1199A allele were significantly increased compared with cells carrying the 1199G allele (p < 0.01). Nevertheless, overexpression of the variant protein (1199A) had no impact on the transport of fluoxetine. ABCB1 encoded by the 1199A mutant allele transports more efficiently escitalopram, citalopram, paroxetine, and sertraline in comparison to the 1199G wild-type allele. This investigation suggests that the 1199A allele drastically increases the activity of P-gp to drive the transport of escitalopram, citalopram, paroxetine, and sertraline in a substrate-specific manner." @default.
• W2892397910 created "2018-10-05" @default.
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• W2892397910 date "2018-12-01" @default.
• W2892397910 modified "2023-09-25" @default.
• W2892397910 title "<i>ABCB1</i> 1199G>A Polymorphism Affects the Intracellular Accumulation of Antidepressants in LLC-PK1 Recombinant Cell Lines" @default.
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• W2892397910 doi "https://doi.org/10.1089/dna.2018.4391" @default.
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