Evidence map›Paper›PMID 36145696›Full record

ArticlePharmaceutics2022

Transport and Permeation Properties of Dapivirine: Understanding Potential Drug-Drug Interactions.

Ruohui Zheng, Guru R Valicherla, Junmei Zhang, Jeremy Nuttall, Peter Silvera, Leslie J Marshall, Philip E Empey, Lisa C Rohan

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

8 authors at 4 institutions in 1 country.

Ruohui ZhengDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.ORCID 0000-0002-5797-8128
Guru R ValicherlaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.ORCID 0000-0002-1180-2530
Junmei ZhangDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.ORCID 0000-0002-5653-2554
Jeremy NuttallInternational Partnership for Microbicides, Silver Spring, MD 20910, USA.ORCID 0000-0003-1346-3357
Peter SilveraAdvanced Bioscience Laboratories, Rockville, MD 20850, USA.
Leslie J MarshallPreclinical Microbicide and Prevention Research Branch, Prevention Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Philip E EmpeyDepartment of Pharmacy & Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.ORCID 0000-0001-7474-2339
Lisa C RohanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.
University of Pittsburgh · USAdvanced Bioscience Laboratories (United States) · USInternational Partnership for Microbicides · USNational Institutes of Health · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
Reproductive Development from Gonads to FetusesT32HD087194 · NICHD · MAGEE-WOMEN'S RES INST AND FOUNDATION · PI ORWIG, KYLE EDWIN · 2017 to 2021
$925k
NCI NIH HHS P30 CA047904NICHD NIH HHS T32 HD087194
6 · The paper itself

Abstract

The dapivirine (DPV) vaginal ring was developed by the nonprofit International Partnership for Microbicides (IPM) for reducing the risk of HIV infection. A clinical study (IPM 028) showed that concomitant use of the DPV ring and miconazole (MIC) altered DPV pharmacokinetic profile. In this work, we investigated whether or not DPV transport and permeation contributed to the observed DPV-MIC interaction. Our study evaluated the interaction between DPV and several transporters that are highly expressed in the human female reproductive tract, including MRP1, MRP4, P-gp, BCRP, and ENT1, using vesicular and cellular systems. We also evaluated the impact of DPV/MIC on cellular tight junctions by monitoring transepithelial electrical resistance with the Ussing chamber. Lastly, we evaluated the effect of MIC on DPV permeability across human cervical tissue. Our findings showed that DPV was not a substrate of MRP1, MRP4, P-gp, BCRP, or ENT1 transporters. Additionally, DPV did not inhibit the activity of these transporters. DPV, MIC, and their combination also did not disrupt cellular tight junctions. MIC did not affect DPV tissue permeability but significantly reduced DPV tissue levels. Therefore, our results suggest that the DPV-MIC interaction is not due to these five transporters, altered tight junction integrity, or altered tissue permeability.

Indexed as

dapivirinedrug-drug interactionsdrug transportersHIVtissue permeability

Identifiers

PMID36145696
PMCPMC9501983
OpenAlexW4296108489

What OpenQuestion holds

Textmetadata
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.