ArticleMolecular pharmaceutics2012
Role of the equilibrative and concentrative nucleoside transporters in the intestinal absorption of the nucleoside drug, ribavirin, in wild-type and Ent1(-/-) mice.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 22 citations in OpenAlex.
- Mechanisms Underlying Cedazuridine-Mediated Enhancement of Oral Decitabine Bioavailability.Cancer research communications · 2026Article
- Evaluation of Ribavirin-Poloxamer Microparticles for Improved Intranasal Absorption.Pharmaceutics · 2021Article
- Loss of ENT1 increases cell proliferation in the annulus fibrosus of the intervertebral disc.Journal of cellular physiology · 2019Article
- Identification of Structural and Molecular Features Involved in the Transport of 3'-Deoxy-Nucleoside Analogs by Human Equilibrative Nucleoside Transporter 3.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.Clinical pharmacokinetics · 2014Review
- Comparison of the permeability of metoprolol and labetalol in rat, mouse, and Caco-2 cells: use as a reference standard for BCS classification.Molecular pharmaceutics · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ribavirin is frontline treatment for hepatitis C virus infection. To determine the role of nucleoside transporters in the intestinal absorption of orally administered ribavirin, we perfused the intestines of Ent1(-/-) and wild-type mice, in situ, with [(3)H] ribavirin (20, 200, and 5000 μM) in the presence and absence of sodium. The decrease in luminal ribavirin concentration over 30 min was measured at 5 min intervals. Blood samples were collected approximately every 10 min. Ribavirin plus phosphorylated metabolite concentrations (hereafter referred to as ribavirin) were determined in tissue, blood, and plasma by HPLC fractionation and scintillation counting. There was no significant difference between wild-type and Ent1(-/-) mice in intestinal loss of ribavirin at any ribavirin concentration studied. Perfusions without sodium drastically reduced the intestinal loss of ribavirin in both wild-type and Ent1(-/-) mice. After 20 μM ribavirin perfusions, Ent1(-/-) intestinal tissue contained 8-fold greater ribavirin than wild-type mice (p < 0.01). Ribavirin concentrations in the wild-type intestinal tissue were 70-fold higher after 200 vs 20 μM perfusions (p < 0.001), indicating saturation of intestinal ribavirin efflux and possibly other processes as well. Ribavirin plasma concentrations were significantly higher in wild-type mice (2.7-fold) vs Ent1(-/-) mice at 30 min after the 20 μM perfusion (p < 0.01). These results suggest that, at lower intestinal concentrations of ribavirin, concentrative and equilibrative nucleoside transporters are important in the intestinal absorption of ribavirin. At higher intestinal concentrations, these transporters are saturated and other processes in the intestine (transport and/or metabolism) play an important role in the absorption of ribavirin.
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