Skip to main content
  • Poster presentation
  • Open access
  • Published:

Vicriviroc, A Novel CCR5 Inhibitor, is NOT A p-glycoprotein Substrate In Vitro

The CCR5 chemokine receptor is a promising target for antiretroviral therapy because of its role as a coreceptor for HIV entry and propagation of infection. Vicriviroc, a small molecule CCR5 inhibitor being studied in clinical trials, is well absorbed in rats and monkeys; in vitro studies were performed with caco-2 cells to determine its bi-directional permeability and potential as a p-glycoprotein (pGp) efflux substrate.

Caco-2 cells (passage 60 to 61) were grown for 3 weeks to confluency and the integrity of the monolayer was confirmed by TEER measurements in the presence of vicriviroc (50 to 400 mM). For bi-directional permeability studies, vicriviroc was placed on either the apical (A) or basolateral (B) compartment at a concentration of 40 mM and permeability (n = 3) was determined over 2 hrs with an LC/MS/MS assay. Total recovery exceeded 85% in all studies. The passive permeability (A to B) performance of the caco-2 cell monolayers were confirmed with atenolol (Pc = 3 ± 1.7 nm/s) and pindolol (Pc = 200 ± 9 nm/s). Functional expression of pGp was confirmed with the standard pGp substrate digoxin (bi-directional efflux ratios: 4- to 10-fold).

Vicriviroc showed high A to B permeability (Pc = 400 ± 4 nm/s) consistent with its high in vivo oral absorption. The bi-directional efflux ratio of vicriviroc was only 0.6 indicating that it is not a pGp substrate in vitro. These data suggested that pGp is unlikely to affect the oral absorption of vicriviroc and that co-administration of vicriviroc with a pGp inhibitor is unlikely to cause significant drug-drug interactions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheng Li.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Li, C., Keung, A., Morrison, R.A. et al. Vicriviroc, A Novel CCR5 Inhibitor, is NOT A p-glycoprotein Substrate In Vitro. Retrovirology 2 (Suppl 1), P158 (2005). https://doi.org/10.1186/1742-4690-2-S1-P158

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1742-4690-2-S1-P158

Keywords