Comparison of bidirectional lamivudine and zidovudine transport using MDCK, MDCK-MDR1, and Caco-2 cell monolayers

J Pharm Sci. 2009 Nov;98(11):4413-9. doi: 10.1002/jps.21744.


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 P(app) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Acridines / pharmacology
  • Animals
  • Biological Availability
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Cell Membrane Permeability / drug effects*
  • Cells, Cultured
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Resistance, Multiple
  • Humans
  • Lamivudine / pharmacokinetics*
  • Lamivudine / pharmacology*
  • Tetrahydroisoquinolines / pharmacology
  • Zidovudine / pharmacokinetics*
  • Zidovudine / pharmacology*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Acridines
  • Tetrahydroisoquinolines
  • Lamivudine
  • Zidovudine
  • Elacridar