Evidence map›Paper›PMID 31081036›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

Increased tenofovir monoester concentrations in patients receiving tenofovir disoproxil fumarate with ledipasvir/sofosbuvir.

Kristina M Brooks, Jose R Castillo-Mancilla, Joshua Blum, Ryan Huntley, Samantha MaWhinney, Keisha Alexander, Becky Jo Kerr, Lucas Ellison, Lane R Bushman, Christine E MacBrayne and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 15 citations in OpenAlex.

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  10. Investigation of the effect of verapamil on the regional absorption of sofosbuvir from rabbit intestine in situ.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Kristina M BrooksDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Jose R Castillo-MancillaDepartment of Medicine, School of Medicine, University of Colorado AMC, Aurora, CO, USA.
Joshua BlumDenver Health, Denver, CO, USA.
Ryan HuntleyDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Samantha MaWhinneyDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado AMC, Aurora, CO, USA.
Keisha AlexanderDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Becky Jo KerrDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Lucas EllisonDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Lane R BushmanDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Christine E MacBrayneDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Peter L AndersonDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
Jennifer J KiserDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus (AMC), Aurora, CO, USA.
University of Colorado Anschutz Medical Campus · USColorado School of Public Health · USDenver Health Medical Center · USUniversity of Colorado Denver · US

Funding

NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Antiviral pharmacology and adherence in drug usersR01DA040499 · NIDA · UNIVERSITY OF COLORADO DENVER · PI KISER, JENNIFER JUSTICE · 2015 to 2019
$2.6M
NCATS NIH HHS UL1 TR002535NIDA NIH HHS R01 DA040499
6 · The paper itself

Abstract

backgroundIntracellular tenofovir diphosphate concentrations are markedly increased in HIV/HCV coinfected individuals receiving tenofovir disoproxil fumarate (TDF) with sofosbuvir-containing treatment. Sofosbuvir may inhibit the hydrolysis of TDF to tenofovir, resulting in increased concentrations of the disoproxil or monoester forms, which may augment cell loading. We sought to quantify tenofovir disoproxil and monoester concentrations in individuals receiving TDF with and without ledipasvir/sofosbuvir.

methodsHIV/HCV coinfected participants receiving TDF-based therapy were sampled pre-dose and 1 and 4 h post-dose prior to and 4 weeks after initiating ledipasvir/sofosbuvir. Tenofovir disoproxil was not detectable. Tenofovir monoester in plasma and tenofovir diphosphate in PBMC and dried blood spots (DBS) were quantified using LC-MS/MS. Geometric mean ratios (week 4 versus baseline) and 95% CIs were generated for the pharmacokinetic parameters. P values reflect paired t-tests.

resultsTen participants had complete data. At baseline, geometric mean (95% CI) tenofovir monoester plasma concentrations at 1 and 4 h post-dose were 97.4 ng/mL (33.0-287.5) and 0.74 ng/mL (0.27-2.06), respectively. With ledipasvir/sofosbuvir, tenofovir monoester concentrations at 4 h post-dose were 5.02-fold higher (95% CI 1.40-18.05; P = 0.019), but did not significantly differ at 1 h post-dose (1.72-fold higher, 95% CI 0.25-11.78; P = 0.54), possibly due to absorption variability. Tenofovir diphosphate in PBMC and DBS were increased 2.80-fold (95% CI 1.71-4.57; P = 0.001) and 7.31-fold (95% CI 4.47-11.95; P < 0.0001), respectively, after 4 weeks of ledipasvir/sofosbuvir.

conclusionsTenofovir monoester concentrations were increased in individuals receiving TDF with ledipasvir/sofosbuvir, consistent with inhibition of TDF hydrolysis. Additional studies are needed to determine the clinical relevance of this interaction.

Indexed as

AdenineAdolescentAdultAntiviral AgentsBenzimidazolesBlood Chemical AnalysisChromatography, LiquidDrug InteractionsFemaleFluorenesHepatitis C, ChronicHIV InfectionsHumansMaleMiddle AgedPhosphorous Acids9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenineAdenineAntiviral AgentsBenzimidazolesFluorenesledipasvirPhosphorous AcidsSofosbuvirTenofovir

Identifiers

PMID31081036
PMCPMC6640288
OpenAlexW2946125756

What OpenQuestion holds

Textmetadata
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Registered trials

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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.