Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26169552
DOI
10.1016/j.reprotox.2015.07.070
PII: S0890-6238(15)30001-0
Knihovny.cz E-resources
- Keywords
- Abacavir, Breast cancer resistance protein, HIV, Multidrug resistance-associated proteins, P-glycoprotein, Transplacental pharmacokinetics,
- MeSH
- Anti-Retroviral Agents pharmacokinetics MeSH
- Madin Darby Canine Kidney Cells MeSH
- Dideoxynucleosides pharmacokinetics MeSH
- Humans MeSH
- Placenta metabolism MeSH
- Rats, Wistar MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins metabolism MeSH
- Dogs MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Dogs MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- abacavir MeSH Browser
- ABCC2 protein, human MeSH Browser
- Anti-Retroviral Agents MeSH
- Dideoxynucleosides MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins MeSH
Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.
References provided by Crossref.org
Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
