Trial reportAntimicrobial agents and chemotherapy2005
Measurement of intracellular didanosine and tenofovir phosphorylated metabolites and possible interaction of the two drugs in human immunodeficiency virus-infected patients.
Trial report in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
39 citing papers in PubMed, 111 citations in OpenAlex.
- Tenofovir-diphosphate in peripheral blood mononuclear cells during low, medium and high adherence to emtricitabine/ tenofovir alafenamide vs. emtricitabine/ tenofovir disoproxil fumarate.AIDS (London, England) · 2021Trial
- Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks (HPTN 066).AIDS research and human retroviruses · 2016Trial
- Single dose pharmacokinetics of oral tenofovir in plasma, peripheral blood mononuclear cells, colonic tissue, and vaginal tissue.AIDS research and human retroviruses · 2013Trial
- Plasma and intracellular population pharmacokinetic analysis of tenofovir in HIV-1-infected patients.Antimicrobial agents and chemotherapy · 2011Trial
- Plasma and intracellular tenofovir pharmacokinetics in the neonate (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
- 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
- A Cross-Biomeasure Study to Optimize Antiretroviral Adherence Estimation.Journal of acquired immune deficiency syndromes (1999) · 2025Article
- Cocaine regulates antiretroviral therapy CNS access through pregnane-x receptor-mediated drug transporter and metabolizing enzyme modulation at the blood brain barrier.Fluids and barriers of the CNS · 2024Article
- Population pharmacokinetics of tenofovir, emtricitabine and intracellular metabolites in transgender women.British journal of clinical pharmacology · 2022Article
- Pharmacogenomics of Antiretroviral Drug Metabolism and Transport.Annual review of pharmacology and toxicology · 2021Review
- Broad spectrum antiviral nucleosides-Our best hope for the future.Annual reports in medicinal chemistry · 2021Article
- Direct and indirect quantification of phosphate metabolites of nucleoside analogs in biological samples.Journal of pharmaceutical and biomedical analysis · 2020Review
- SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells.Scientific reports · 2017Article
- Model Linking Plasma and Intracellular Tenofovir/Emtricitabine with Deoxynucleoside Triphosphates.PloS one · 2016Observational
- Pharmacokinetics and preliminary safety study of pod-intravaginal rings delivering antiretroviral combinations for HIV prophylaxis in a macaque model.Antimicrobial agents and chemotherapy · 2014Article
- Tenofovir, emtricitabine, and tenofovir diphosphate in dried blood spots for determining recent and cumulative drug exposure.AIDS research and human retroviruses · 2013Article
- The clinical pharmacology of antiretrovirals for HIV prevention.Current opinion in HIV and AIDS · 2012Review
- Safety and pharmacokinetics of intravaginal rings delivering tenofovir in pig-tailed macaques.Antimicrobial agents and chemotherapy · 2012Article
- Compared to subcutaneous tenofovir, oral tenofovir disoproxyl fumarate administration preferentially concentrates the drug into gut-associated lymphoid cells in simian immunodeficiency virus-infected macaques.Antimicrobial agents and chemotherapy · 2012Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent work has demonstrated the existence of a systemic interaction between didanosine (ddI) and tenofovir disoproxyl fumarate (TDF) that leads to a significant increase in plasma ddI levels when coadministered with TDF (40 to 50% increase). These two drugs are, respectively, nucleoside and nucleotide analogues of adenosine and efficiently inhibit the human immunodeficiency virus (HIV) reverse transcriptase when transformed to their triphosphate moieties in the intracellular (IC) medium (ddA-TP and TFV-DP, respectively). Since ddI and TDF partly share the same IC metabolic pathway leading to the active triphosphates, we investigated a putative IC interaction. We used high-performance liquid chromatography-tandem mass spectrometry techniques to determine ddA-TP and TFV-DP IC levels in HIV-infected patients cotreated with both drugs, in comparison with patients treated with just one of the two drugs. These measurements revealed no significant differences in IC levels of the corresponding triphosphates when ddI (250 mg, once a day [QD]) was coadministered with TDF (300 mg, QD) compared to ddI 400 mg (QD) administered without TDF, thus supporting the dose adaptation proposed for this combination. However, we observed that both ddA-TP and TFV-DP have very long IC half-lives, resulting in unusual IC pharmacokinetic profiles with no significant changes in triphosphate concentrations between two dosings. In the case of TFV-DP, this t(1/2) of elimination was roughly estimated to be 180 h (7.5 days). This characteristic is certainly interesting in terms of efficacy but could have some drawbacks in terms of virus resistance for patients discontinuing these drugs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.