ArticleMolecular medicine reports2018
Involvement of multidrug resistance protein 4 in the hepatocyte efflux of lamivudine and entecavir.
Article in Molecular medicine reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Recapitulating gestational progression: a high-throughput 3D bioprinted vascularized human placenta demonstrating stage-specific molecular and functional signatures of human pregnancy.Scientific reports · 2026Article
- Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection.Antimicrobial agents and chemotherapy · 2024Article
- Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas.Antioxidants (Basel, Switzerland) · 2021Article
- New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection: Increase of entecavir dosage.World journal of gastroenterology · 2021Review
- Important roles of transporters in the pharmacokinetics of anti-viral nucleoside/nucleotide analogs.Expert opinion on drug metabolism & toxicologyArticle
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance protein 4 (MRP4) is capable of transporting acyclic nucleotide phosphonates, but little is known about its role in lamivudine (LAM) and entecavir (ETV) transport. In the present study, the involvement of MRP4 in the transport of LAM and ETV was investigated through in vitro experiments. The cytotoxicity of three antiviral drugs and their activities against HBV as characterized in HepG2.4D14 [wild‑type hepatitis B virus (HBV)] and HepG2.A64 (ETV‑resistant HBV) cells. LAM, ETV and tenofovir (TFV) demonstrated a 50% effective concentration against HBV of 4.14±0.03, 0.13±0.02 and 3.24±0.01 µM in HepG2.4D14 cells and of 5.94±0.20, 6.28±0.07 and 11.43±0.09 µM in HepG2.A64 cells, respectively. After administering 3-([(3-(2-[7-chloro-2-quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoporphyl)-thio)-methyl]-thio) propanoic acid (MK571), the intracellular concentrations of all three drugs were much lower than the extracellular drug concentrations in these two cell types, whereas the intracellular drug concentrations in wild‑type cells were higher than those in ETV‑resistant cells. Furthermore, the intracellular levels of LAM, ETV and TFV were enhanced and the extracellular concentrations were reduced by addition of MK571. Thus, MRP4 is mainly responsible for the efflux of LAM and ETV in hepatocyte cultures. These results may contribute to enhancing antiviral efficacy.
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