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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 [3H] 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 riba...
| Authors: | Aaron M. Moss; Christopher J. Endres; Ana Ruiz-Garcia; Doo-Sup Choi; Jashvant D. Unadkat | |
| Journal: | Molecular Pharmaceutics | |
| Year: | 2012 | |
| DOI: | 10.1021/mp200647a | |
| Publication date: | 03-08-2012 |
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