Transport of Lamivudine [(-)-β-l-2′,3′-Dideoxy-3′-thiacytidine] and High-Affinity Interaction of Nucleoside Reverse Transcriptase Inhibitors with Human Organic Cation Transporters 1, 2, and 3

@article{Minuesa2009TransportOL,
  title={Transport of Lamivudine [(-)-$\beta$-l-2′,3′-Dideoxy-3′-thiacytidine] and High-Affinity Interaction of Nucleoside Reverse Transcriptase Inhibitors with Human Organic Cation Transporters 1, 2, and 3},
  author={Gerard Minuesa and Christopher Volk and Miriam Molina-Arcas and Valentin Gorboulev and Itziar Erkizia and Petra Arndt and Bonaventura Clotet and Marçal Pastor-Anglada and Hermann Koepsell and Javier Martinez-Picado},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2009},
  volume={329},
  pages={252 - 261}
}
Nucleoside reverse transcriptase inhibitors (NRTIs) need to enter cells to act against the HIV-1. Human organic cation transporters (hOCT1–3) are expressed and active in CD4+ T cells, the main target of HIV-1, and have been associated with antiviral uptake in different tissues. In this study, we examined whether NRTIs interact and are substrates of hOCT in cells stably expressing these transporters. Using [3H]N-methyl-4-phenylpyridinium, we found a high-affinity interaction among abacavir [[(1S… Expand
Interactions of Tenofovir, Lamivudine, Abacavir and Didanosine in Primary Human Cells
TLDR
The high failure rates seen with TDF, ABC and 3TC are not fully explained by an interaction at transporter level, and may be at the level of drug transport. Expand
Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE, Mate)
TLDR
Data suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate transporters, which can engage in drug-drug interactions that reduce renal excretion of co-administered substrates and enhance their retention in the kidneys, potentially compromising therapeutic safety. Expand
Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions
TLDR
Data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level. Expand
Interaction Studies of Resolvin E1 Analog (RX-10045) with Efflux Transporters.
TLDR
Uptake studies in human corneal epithelial cells suggest that RX-10045 is a strong inhibitor of organic cation transporter-1 (OCT-1) and the resolvin analog was identified as a substrate/inhibitor for efflux transporters (MRP2 and BCRP). Expand
Evaluation and Prediction of Potential Drug-Drug Interactions of Linagliptin Using In Vitro Cell Culture Methods
TLDR
A panel of stably and transiently transfected cell lines was used to elucidate the carrier-mediated transport processes that are involved in linagliptin disposition in vivo and to assess the potential for drug-drug interactions (DDIs). Expand
Inhibitory and facilitory actions of isocyanine derivatives at human and rat organic cation transporters 1, 2 and 3: a comparison to human alpha 1- and alpha 2-adrenoceptor subtypes.
TLDR
D24, other isocyanine congeners and chemically-related adrenergic agents inhibit OCT-mediated [3H]MPP+ transport, and all drugs display significant activity at alpha1- and alpha2- adrenoceptor subtypes, expanding previous reports of promiscuity between pharmacophores recognising alpha-adrenoceptors and OCTs. Expand
Organic cation transporters OCT1 and OCT2 determine the accumulation of lamivudine in CD4 cells of HIV-infected patients
TLDR
A role of OCT1 and OCT2 is indicated for the cellular accumulation of lamivudine in HIV-infected individuals. Expand
Uptake Transporters of Nucleoside-Derived Anti-HIV Drugs: Expression and Functional Analysis in Immune Cells
The present thesis has addressed the question of which mechanisms take part in the entry of the Nucleoside Reverse Transcriptase Inhibitors (NBTIs) used in HIV therapy, focusing our studies on theExpand
Rat Organic Cation Transporter 1 Contains Three Binding Sites for Substrate 1-Methyl-4-phenylpyridinium per Monomer
TLDR
Measurement of the binding and transport of model substrate 1-methyl-4-phenylpyridinium+ (MPP+) by cell-free-expressed fusion proteins of rOCT1 and rO CT1 mutants with green fluorescent protein that had been reconstituted into nanodiscs or proteoliposomes suggests that the low-affinity sites are involved in MPP+ transport, whereas high-aff Trinity binding influences transport allosterically. Expand
Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters
TLDR
It is suggested that MATE1 might cause DDI between emtricitabine and other co-administrated drugs including antiretrovirals. Expand
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