Comparison of bidirectional lamivudine and zidovudine transport using MDCK, MDCK-MDR1, and Caco-2 cell monolayers.
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Data
2009
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Resumo
Bidirectional transport studies were conducted using Caco-2, MDCK, and
MDCK–MDR1 to determine P-gp influences in lamivudine and zidovudine permeability
and evaluate if zidovudine permeability changes with the increase of zidovudine
concentration and/or by association of lamivudine. Transport of lamivudine and zidovudine
separated and coadministrated across monolayers based on these cells were
quantified using LC–MS–MS. Drug efflux by P-gp was inhibited using GG918. Bidirectional
transport of lamivudine and zidovudine was performed across MDCK–MDR1 and
Caco-2 cells. Statistically significant transport decrease in B!A direction was observed
using MDCK–MDR1 for zidovudine and MDCK–MDR1 and Caco-2 for lamivudine.
Results show increased transport in B!A and A!B directions as concentration
increases but data from Papp increase in both directions for both drugs in Caco-2,
decrease in MDCK, and does not change significantly in MDCK–MDR1. Zidovudine
transport in A!B direction increases when coadministrated with increasing lamivudine
concentration but does not change significantly in B!A direction. Zidovudine
and lamivudine are P-gp substrates, but results assume that P-gp does not affect
significantly lamivudine and zidovudine. Their transport in monolayers based on
Caco-2 cells increase proportionally to concentration (in both directions) and zidovudine
transport in Caco-2 cell monolayer does not show significant changes with lamivudine
increasing concentrations.
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Permeability, Bioavailability, P-glycoprotein, Passive diffusion, Efflux pumps
Citação
SOUZA, J. de et al. Comparison of bidirectional lamivudine and zidovudine transport using MDCK, MDCK-MDR1, and Caco-2 cell monolayers. Journal of Pharmaceutical Sciences, v. 98, p. 4413-4419, 2009. Disponível em: <https://www.sciencedirect.com/science/article/abs/pii/S0022354915329580?via%3Dihub>. Acesso em: 10 jan. 2017.