Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F16%3A10325097" target="_blank" >RIV/00216208:11150/16:10325097 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0006295216301666" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0006295216301666</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2016.07.001" target="_blank" >10.1016/j.bcp.2016.07.001</a>
Alternative languages
Result language
angličtina
Original language name
Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir
Original language description
Adefovir, an acyclic nucleotide reverse transcriptase inhibitor used to treat hepatitis B viral infection, is primarily eliminated renally through cooperation of glomerular filtration with active tubular transport. Nonalcoholic steatohepatitis is a variable in drug disposition, yet the impact on renal transport processes has yet to be fully understood. The goal of this study was to determine the effect of nonalcoholic steatohepatitis on the pharmacokinetics of adefovir in rats given a control or methionine and choline deficient diet to induce nonalcoholic steatohepatitis. Animals received a bolus dose of 7mg/kg (35uCi/kg) [(3)H] adefovir with consequent measurement of plasma and urine concentrations. Inulin clearance was used to determine glomerular filtration rate. Methionine and choline deficient diet-induced nonalcoholic steatohepatitis prolonged the elimination half-life of adefovir. This observation occurred in conjunction with reduced distribution volume and hepatic levels of adefovir. Notably, despite these changes, renal clearance and overall clearance were not changed, despite markedly reduced glomerular filtration rate in nonalcoholic steatohepatitis. Alteration of glomerular filtration rate was fully compensated for by a significant increase in tubular secretion of adefovir. Analysis of renal transporters confirmed transcriptional up-regulation of Mrp4, the major transporter for adefovir tubular secretion. This study demonstrates changes to glomerular filtration and tubular secretion that alter pharmacokinetics of adefovir in nonalcoholic steatohepatitis. Nonalcoholic steatohepatitis-induced changes in renal drug elimination processes could have major implications in variable drug response and the potential for toxicity.
Czech name
—
Czech description
—
Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
—
Result continuities
Project
<a href="/en/project/EE2.3.30.0061" target="_blank" >EE2.3.30.0061: Increasing of the R&D capacity at Charles University through new positions for graduates of doctoral studies</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Pharmacology
ISSN
0006-2952
e-ISSN
—
Volume of the periodical
115
Issue of the periodical within the volume
September
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
144-151
UT code for WoS article
000381545700015
EID of the result in the Scopus database
2-s2.0-84980369138