Evidence map›Paper›PMID 29802984›Full record

ArticleEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2019

Development of rectal enema as microbicide (DREAM): Preclinical progressive selection of a tenofovir prodrug enema.

Thuy Hoang, Abhijit A Date, Jairo Ortiz Ortiz, Ting-Wei Young, Sabrine Bensouda, Peng Xiao, Mark Marzinke, Lisa Rohan, Edward J Fuchs, Craig Hendrix and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. 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

15 authors at 4 institutions in 1 country.

Thuy HoangThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA.
Abhijit A DateThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.
Jairo Ortiz OrtizThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.
Ting-Wei YoungThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA.
Sabrine BensoudaThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peng XiaoNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
Mark MarzinkeDepartment of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lisa RohanDepartment of Pharmaceutical Sciences, University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, PA, USA.
Edward J FuchsDepartment of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Craig HendrixDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sanjeev GumberDivision of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Francois VillingerNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
Richard A ConeThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.
Justin HanesThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA. Electronic address: hanes@jhmi.edu.
Laura M EnsignThe Center for Nanomedicine at the Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA. Electronic address: lensign@jhmi.edu.
Johns Hopkins University · USUniversity of Louisiana at Lafayette · USEmory University · USUniversity of Pittsburgh · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
UH Hilo COP A&RP20GM103466 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI HELEN C TURNER · 2012 to 2026
$60.3M
The Role of gp120 on Cardiovascular Disease in People Living with HIVU54MD007601 · NIMHD · UNIVERSITY OF HAWAII AT MANOA · PI Benjamin C. Fogelgren · 2017 to 2026
$59.5M
TRPA1 Physiology in Diabetes, Metabolic Syndrome, and MetabolismP20GM113134 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI Michael A. Ortega · 2017 to 2026
$21.5M
Tissue pharmacology imaging and modelingU19AI113127 · NIAID · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S. · 2014 to 2018
$20.7M
Mucus-Penetrating Nanoparticle Containing Enemas for Ulcerative ColitisR01DK107806 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ENSIGN, LAURA, HANES, JUSTIN S. · 2016 to 2019
$1.5M
NIAID NIH HHS P30 AI094189NIAID NIH HHS U19 AI113127NIDDK NIH HHS R01 DK107806NIGMS NIH HHS P20 GM103466NIGMS NIH HHS P20 GM113134NIH HHS P51 OD011132NIMHD NIH HHS U54 MD007601
6 · The paper itself

Abstract

HIV pre-exposure prophylaxis (PrEP) strategies have the potential to prevent millions of incident HIV infections each year. However, the efficacy of PrEP strategies has been plagued by issues of non-adherence, likely because of the difficulty in motivating otherwise healthy people to adhere to treatment regimens that require significant behavioral changes and daily discipline. An alternative approach to PrEP is to focus on strategies that fit in to normal, and even desirable, sexual behaviors, such as the use of cleansing enemas by men who have sex with men (MSM) prior to receptive anal intercourse (RAI). Here, we describe preclinical efforts toward optimizing a tenofovir (TFV)-based enema formulation for rectal PrEP. Using a murine model, we compared the plasma and tissue pharmacokinetics of TFV and various TFV prodrugs, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and hexadecyloxypropyl tenofovir (CMX157), after dosing as enema formulations with varying osmolality and ion content. We observed that the enema vehicle composition played a more important role than the TFV prodrug properties in achieving rapid and therapeutically relevant tenofovir diphosphate (TFV-DP) concentrations in mouse colorectal tissue. Our results support the next steps, which are further preclinical (non-human primate) and clinical development of a hypo-osmolar TFV enema product for rectal PrEP.

Indexed as

Anti-Infective AgentsProdrugsRectumTenofovirAdenineAdministration, RectalAlanineAnimalsAnti-HIV AgentsEnemaHIV-1HIV InfectionsHomosexuality, MaleMaleMiceOrganophosphatesAdenineAlanineAnti-HIV AgentsAnti-Infective Agentshexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenineOrganophosphatesOrganophosphonatesProdrugsTenofovirtenofovir alafenamidetenofovir diphosphateFleetHypotonicRectal doucheRectal gelSodium bicarbonate

Identifiers

PMID29802984
PMCPMC6428633
OpenAlexW2803140811

What OpenQuestion holds

Textmetadata
LicenceTDM
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.