Trial reportPloS one2014
A multi-compartment single and multiple dose pharmacokinetic comparison of rectally applied tenofovir 1% gel and oral tenofovir disoproxil fumarate.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00984971 (A Two-site, Phase 1, Partially-blinded, Placebo-controlled Safety, Acceptability and Pharmacokinetic Trial of Topical, Vaginally-formulated Tenofovir 1% Gel Applied Rectally Compared With Oral 300 mg Tenofovir Disoproxil Fumarate in HIV-1 Seronegative Adults), which is not on this map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Two-site, Phase 1, Partially-blinded, Placebo-controlled Safety, Acceptability and Pharmacokinetic Trial of Topical, Vaginally-formulated Tenofovir 1% Gel Applied Rectally Compared With Oral 300 mg Tenofovir Disoproxil Fumarate in HIV-1 Seronegative Adults
Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir Vaginal Film and Gel Formulation (FAME 05).Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.The Journal of infectious diseases · 2017Trial
- MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Trial
- Trial
- A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.The Journal of infectious diseases · 2016Trial
- Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women.AIDS research and human retroviruses · 2016Trial
- Simultaneous Evaluation of Safety, Acceptability, Pericoital Kinetics, and Ex Vivo Pharmacodynamics Comparing Four Rectal Microbicide Vehicle Candidates.AIDS research and human retroviruses · 2015Trial
- Trial
- Mucosal tenofovir 1% gel stimulates cell proliferation and type I/III interferon pathways.Microbiology spectrum · 2026Article
- Optimizing On-Demand Tenofovir Disoproxil Fumarate/Emtricitabine Dosing in Women for HIV Prevention.The Journal of infectious diseases · 2026Article
- The predictive value of macaque models of preexposure prophylaxis for HIV prevention.Current opinion in HIV and AIDS · 2022Review
- Development of rectal enema as microbicide (DREAM): Preclinical progressive selection of a tenofovir prodrug enema.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Article
- The Pre-clinical Toolbox of Pharmacokinetics and Pharmacodynamics:Frontiers in pharmacology · 2019Review
- MALDI Mass Spectrometry Imaging Reveals Heterogeneous Distribution of Tenofovir and Tenofovir Diphosphate in Colorectal Tissue of Subjects Receiving a Tenofovir-Containing Enema.The Journal of pharmacology and experimental therapeutics · 2018Article
- Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography.Drug delivery and translational research · 2018Article
- Heterogeneity of HIV-1 Replication in Ectocervical and Vaginal Tissue Ex Vivo.AIDS research and human retroviruses · 2018Article
- The Safety of Multiple Flexible Sigmoidoscopies with Mucosal Biopsies in Healthy Clinical Trial Participants.AIDS research and human retroviruses · 2017Article
- Historical development of vaginal microbicides to prevent sexual transmission of HIV in women: from past failures to future hopes.Drug design, development and therapy · 2017Review
- Multicompartmental Pharmacokinetic Model of Tenofovir Delivery to the Rectal Mucosa by an Enema.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blood, colonic biopsies and rectal and vaginal mucosal fluids were collected after the single oral TDF, the single topical TFV gel dose, and after 7 days of topical TFV gel dosing for extracellular analysis of TFV and intracellular analysis of the active metabolite tenofovir diphosphate (TFVdp) in peripheral blood mononuclear cells (PBMCs) and isolated mucosal mononuclear cells (MMC), including CD4+ and CD4- cell subsets. With a single rectal dose, TFV plasma concentrations were 24–33 fold lower and half-life was 5 h shorter compared to a single oral dose (p = 0.02). TFVdp concentrations were also undetectable in PBMCs with rectal dosing. Rectal tissue exposure to both TFV and TFVdp was 2 to 4-log10 higher after a single rectal dose compared to a single oral dose, and after 7 daily doses, TFVdp accumulated 4.5 fold in tissue. TFVdp in rectal tissue homogenate was predictive (residual standard error, RSE = 0.47) of tissue MMC intracellular TFVdp concentration, with the CD4+ cells having a 2-fold higher TFVdp concentration than CD4- cells. TFV concentrations from rectal sponges was a modest surrogate indicator for both rectal tissue TFV and TFVdp (RSE = 0.67, 0.66, respectively) and plasma TFV (RSE = 0.38). TFV penetrates into the vaginal cavity after oral and rectal dosing, with rectal dosing leading to higher vaginal TFV concentrations (p<0.01). Trial registration: ClinicalTrials.gov NCT00984971.
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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.