ArticleAntimicrobial agents and chemotherapy2007
Evidence and possible consequences of the phosphorylation of nucleoside reverse transcriptase inhibitors in human red blood cells.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Plasma and intracellular tenofovir pharmacokinetics in the neonate (ANRS 12109 trial, step 2).Antimicrobial agents and chemotherapy · 2011Trial
- Very high concentrations of active intracellular phosphorylated emtricitabine in neonates (ANRS 12109 trial, step 2).Antimicrobial agents and chemotherapy · 2011Trial
- Intracellular nucleotide levels during coadministration of tenofovir disoproxil fumarate and didanosine in HIV-1-infected patients.Antimicrobial agents and chemotherapy · 2011Trial
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- A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation.Journal of acquired immune deficiency syndromes (1999) · 2025Article
- Rapid Enzymatic Assay for Antiretroviral Drug Monitoring Using CRISPR-Cas12a-Enabled Readout.ACS synthetic biology · 2025Article
- Gender Affirming Hormones Do Not Affect the Exposure and Efficacy of F/TDF or F/TAF for HIV Preexposure Prophylaxis: A Subgroup Analysis from the DISCOVER Trial.Transgender health · 2024Article
- Peripheral blood mononuclear cells isolation from mouse and rabbit blood to quantify active nucleotide and define brincidofovir dose for smallpox.Bioanalysis · 2024Review
- Immunoregulatory molecule expression on extracellular microvesicles in people living with HIV.Frontiers in immunology · 2024Article
- Article
- REverSe TRanscrIptase chain termination (RESTRICT) for selective measurement of nucleotide analogs used in HIV care and prevention.Bioengineering & translational medicine · 2023Article
- Antiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and Humans.Antimicrobial agents and chemotherapy · 2020Article
- Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Levels.ACS sensors · 2020Article
- Direct and indirect quantification of phosphate metabolites of nucleoside analogs in biological samples.Journal of pharmaceutical and biomedical analysis · 2020Review
- Simultaneous determination of intracellular concentrations of tenofovir, emtricitabine, and dolutegravir in human brain microvascular endothelial cells using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Analytica chimica acta · 2019Article
- Tenofovir Diphosphate in Dried Blood Spots Is Strongly Associated With Viral Suppression in Individuals With Human Immunodeficiency Virus Infections.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Observational
- Multiscale Systems-Pharmacology Pipeline to Assess the Prophylactic Efficacy of NRTIs Against HIV-1.CPT: pharmacometrics & systems pharmacology · 2016Article
- Development and validation of a dried blood spot assay for the quantification of ribavirin using liquid chromatography coupled to mass spectrometry.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2014Article
- Quantitation of tenofovir and emtricitabine in dried blood spots (DBS) with LC-MS/MS.Journal of pharmaceutical and biomedical analysis · 2014Article
- Organic cation transporters OCT1 and OCT2 determine the accumulation of lamivudine in CD4 cells of HIV-infected patients.Infection · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intracellular metabolism of nucleoside reverse transcriptase inhibitors (NRTI) in mononuclear cells has been thoroughly studied, but that in red blood cells (RBC) has been disregarded. However, the phosphorylation of other analogous nucleosides (in particular, ribavirin) has been described previously. In this study, we investigated for the first time the phosphorylation of NRTI in human RBC. The presence of intracellular zidovudine (AZT) monophosphate, AZT triphosphate, lamivudine (3TC) triphosphate, and tenofovir (TFV) diphosphate, as well as endogenous dATP, dGTP, and dTTP, in RBC collected from human immunodeficiency virus-infected patients was examined. We observed evidence of a selective phosphorylation of 3TC, TFV, and endogenous purine deoxynucleosides to generate their triphosphate moieties. Conversely, no trace of AZT phosphate metabolites was found, and only faint dTTP signals were visible. A comparison of intracellular TFV diphosphate and 3TC triphosphate levels in RBC and peripheral blood mononuclear cells (PBMC) further highlighted the specificity of NRTI metabolism in each cell type. These findings raise the issue of RBC involvement in drug-drug interaction, drug pharmacokinetics, and drug-induced toxicity. Moreover, the typical preparation of PBMC samples by gradient density centrifugation does not prevent their contamination with RBC. We demonstrated that the presence of RBC within PBMC hampers an accurate determination of intracellular TFV diphosphate and dATP levels in clinical PBMC samples. Thus, we recommend removing RBC during PBMC preparation by using an ammonium chloride solution to enhance both the accuracy and the precision of intracellular drug monitoring.
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