ArticleAntimicrobial agents and chemotherapy2004
Role of purine nucleoside phosphorylase in interactions between 2',3'-dideoxyinosine and allopurinol, ganciclovir, or tenofovir.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine.Antimicrobial agents and chemotherapy · 2016Trial
- Intracellular nucleotide levels during coadministration of tenofovir disoproxil fumarate and didanosine in HIV-1-infected patients.Antimicrobial agents and chemotherapy · 2011Trial
- Pilot pharmacokinetic study of human immunodeficiency virus-infected patients receiving tenofovir disoproxil fumarate (TDF): investigation of systemic and intracellular interactions between TDF and abacavir, lamivudine, or lopinavir-ritonavir.Antimicrobial agents and chemotherapy · 2009Trial
- The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers.British journal of clinical pharmacology · 2008Trial
- Measurement of intracellular didanosine and tenofovir phosphorylated metabolites and possible interaction of the two drugs in human immunodeficiency virus-infected patients.Antimicrobial agents and chemotherapy · 2005Trial
- Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection.Antimicrobial agents and chemotherapy · 2022Article
- Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics.Metabolism open · 2021Article
- Nucleotide Reverse Transcriptase Inhibitors: A Thorough Review, Present Status and Future Perspective as HIV Therapeutics.Current HIV research · 2017Review
- Model Linking Plasma and Intracellular Tenofovir/Emtricitabine with Deoxynucleoside Triphosphates.PloS one · 2016Observational
- Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- The role of drug transporters in the kidney: lessons from tenofovir.Frontiers in pharmacology · 2014Review
- Role of the Pharmacist in Caring for Patients with HIV/AIDS: Clinical Practice Guidelines.The Canadian journal of hospital pharmacy · 2012Article
- Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides.PLoS pathogens · 2012Article
- Article
- Use of antineoplastic agents in patients with cancer who have HIV/AIDS.The Lancet. Oncology · 2011Review
- Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action.Clinical pharmacokinetics · 2010Review
- Conserved T cell and natural killer cell function in treatment-experienced adults receiving tenofovir plus didanosine as nucleoside reverse transcription inhibitor backbone.Clinical and experimental immunology · 2009Article
- Intracellular metabolism of the nucleotide prodrug GS-9131, a potent anti-human immunodeficiency virus agent.Antimicrobial agents and chemotherapy · 2008Article
- Evidence and possible consequences of the phosphorylation of nucleoside reverse transcriptase inhibitors in human red blood cells.Antimicrobial agents and chemotherapy · 2007Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The level of systemic exposure to 2',3'-dideoxyinosine (ddI) is increased 40 to 300% when it is coadministered with allopurinol (Allo), ganciclovir (GCV), or tenofovir. However, the mechanism for these drug interactions remains undefined. A metabolic route for ddI clearance is its breakdown by purine nucleoside phosphorylase (PNP). Consistent with previous reports, enzymatic inhibition assays showed that acyclic nucleotide analogs can inhibit the phosphorolysis of inosine. It was further established that the mono- and diphosphate forms of tenofovir were inhibitors of PNP-dependent degradation of ddI (K(i)s, 38 nM and 1.3 microM, respectively). Allo and its metabolites were found to be relatively weak inhibitors of PNP (K(i)s, >100 microM). Coadministration of tenofovir, GCV, or Allo decreased the amounts of intracellular ddI breakdown products in CEM cells, while they increased the ddI concentrations (twofold increase with each drug at approximately 20 microM). While inhibition of the physiological function of PNP is unlikely due to the ubiquitous presence of high levels of enzymatic activity, phosphorylated metabolites of GCV and tenofovir may cause the increased level of exposure to ddI by direct inhibition of its phosphorolysis by PNP. The discrepancy between the cellular activity of Allo and the weak enzyme inhibition by Allo and its metabolites may be explained by an indirect mechanism of PNP inhibition. This mechanism may be facilitated by the unfavorable equilibrium of PNP and the buildup of one of its products (hypoxanthine) through the inhibition of xanthine oxidase by Allo. These findings support the inhibition of PNP-dependent ddI degradation as the molecular mechanism of these drug interactions.
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