Transport of ribavirin across the rat and human placental barrier: roles of nucleoside and ATP-binding cassette drug efflux transporters
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10395619" target="_blank" >RIV/00216208:11160/19:10395619 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=-cqVkXdJIN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=-cqVkXdJIN</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2019.01.024" target="_blank" >10.1016/j.bcp.2019.01.024</a>
Alternative languages
Result language
angličtina
Original language name
Transport of ribavirin across the rat and human placental barrier: roles of nucleoside and ATP-binding cassette drug efflux transporters
Original language description
Ribavirin is a broad-spectrum nucleoside-derived antiviral drug used in combination pharmacotherapy treatment of hepatitis C virus infection. Current evidence indicates that ribavirin-associated teratogenicity is not significant in humans, but more information about the developmental toxicity and mechanisms involved in ribavirin placental kinetics is required to assure its safe use in pregnancy. Thus, we have investigated potential roles of equilibrative nucleoside transporters (ENTs, SLC29A), Na+-dependent influx-mediating concentrative nucleoside transporters (CNTs, SLC28A), and ATP-binding cassette efflux pumps (ABC), in ribavirin placental pharmacokinetics. Our data indicate that ENT1 participates in uptake of ribavirin by BeWo cells, fresh human placental villous fragments and microvillous plasma membrane (MVM) vesicles while activity of CNTs (probably CNT2) was only observed in BeWo cells. In situ dual perfusion experiments with rat term placenta in an open circuit setup showed that ENT inhibition significantly decreases total ribavirin maternal-to-foetal and foetalto- maternal clearances. In contrast, no contribution of ABC transporters, p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), or multidrug resistance-associated protein (ABCC2) was detected in assays with MDCKII cells overexpressing them, or in closed circuit dual perfusion experiments with rat term placenta. In summary, our data show that ribavirin placental pharmacokinetics are largely controlled by ENT1 activity and independent of ABCB1, ABCG2, and ABCC2 efflux pumps.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
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
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Volume of the periodical
163
Issue of the periodical within the volume
May
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
60-70
UT code for WoS article
000466060000006
EID of the result in the Scopus database
2-s2.0-85061191476