Evidence map›Paper›PMID 33547874›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2021

A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.

Priya Jayachandran, Maria Garcia-Cremades, Katarina Vučićević, Namandjé N Bumpus, Peter Anton, Craig Hendrix, Radojka Savić

Open access · goldAbstract readClinical TrialComparative Study
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.1field-weighted citation impact, top 53% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
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

7 authors at 5 institutions in 2 countries.

Priya JayachandranDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Maria Garcia-CremadesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Katarina VučićevićDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Namandjé N BumpusDivision of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Peter AntonUniversity of California Los Angeles, Los Angeles, California, USA.
Craig HendrixDivision of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Radojka SavićDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
University of California, San Francisco · USJohns Hopkins Medicine · USJohns Hopkins University · USUniversity of Belgrade · RSUniversity of California, Los Angeles · US

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Laboratory Center (LC): Microbicide Trials NetworkUM1AI106707 · NIAID · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI MELLORS, JOHN W, ROHAN, LISA CENCIA · 2014 to 2021
$27.1M
Regulatory compliance and human subjects safetyU19AI060614 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HENDRIX, CRAIG WALTER · 2004 to 2009
$19.1M
CLINICAL, PHARMACOLOGY, DRUG ACTION &PHARMACOKINETICST32GM007546 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Radojka Savic · 1985 to 2026
$8.9M
JOHNS HOPKINS CENTER FOR AIDS RESEARCHP30AI042855 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BARTLETT, JOHN G · 2000 to 2005
$7.7M
NIAID NIH HHS P30 AI042855NIAID NIH HHS P30 AI094189NIAID NIH HHS U19 AI060614NIAID NIH HHS UM1 AI106707NIGMS NIH HHS T32 GM007546
6 · The paper itself

Abstract

Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV-1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4.

Indexed as

Administration, OralAdministration, RectalAdultAgedAnti-HIV AgentsBiological AvailabilityDrug DevelopmentFemaleGelsHIV Core Protein p24HIV InfectionsHIV SeronegativityHumansLeukocytes, MononuclearMaleMiddle AgedAnti-HIV AgentsGelsHIV Core Protein p24Tenofovir

Identifiers

PMID33547874
PMCPMC7965838
OpenAlexW3126431573

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.