Linked Life Data

19602549

Source:http://linkedlifedata.com/resource/pubmed/id/19602549

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-9-23
pubmed:abstractText
Ribavirin [1-(beta-d-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide] is the treatment of choice for hepatitis C virus infection. Ribavirin is a substrate of several nucleoside transporters, including the equilibrative nucleoside transporter (Ent) and the concentrative nucleoside transporter 2. To determine the role of Ent1 in ribavirin absorption and erythrocyte distribution, we examined its pharmacokinetics in Ent1-null mice. After intravenous administration, we found that the erythrocyte area under the curve (AUC(0-12 h)) was reduced 3.05-fold along with 2.63-fold reduction of erythrocyte versus plasma AUC ratio in the Ent1(-/-) mice, whereas there was no significant difference in the plasma AUC(0-12 h) between Ent1(+/+) and Ent1(-/-) mice. After 48 h, we found a similar fraction of ribavirin or total radioactivity excreted in the urine between the Ent1(+/+) and Ent1(-/-) mice. After oral administration of three different doses, 0.024, 0.24, and 6.1 mg/kg, we found that the dose-normalized plasma AUC(0-12 h) of ribavirin was 69.7 +/- 12.0, 20.7 +/- 1.5, and 18.3 +/- 2.7 min/l, respectively, in the Ent1(+/+) mice and 18.9 +/- 2.8, 13.0 +/- 0.5, and 12.2 +/- 1.0 min/l, respectively, in the Ent1(-/-) mice. It is interesting that at the highest dose, the dose-normalized plasma AUC(0-30 min), AUC(0-12 h), and C(max) in the Ent1(+/+) mice were decreased 4.0-, 3.8-, and 3.4-fold, respectively, compared with the lowest dose, suggesting absorption was saturated at the highest dose we used. The dose-normalized plasma AUC(0-12 h) was 3.7- and 1.5-fold lower at the lowest and the highest dose, respectively, in the Ent1(-/-) mice compared with those of the Ent1(+/+) mice. Our findings indicate that Ent1 plays a significant role in the oral absorption and erythrocyte distribution of ribavirin.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
331
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
287-96
pubmed:dateRevised
2011-6-14
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The role of nucleoside transporters in the erythrocyte disposition and oral absorption of ribavirin in the wild-type and equilibrative nucleoside transporter 1-/- mice.
pubmed:affiliation
Department of Pharmaceutics, University of Washington, Seattle, 98195, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural