Evidence map›Paper›PMID 34312680›Full record

ArticleThe Journal of antimicrobial chemotherapy2021

Intramuscular and subcutaneous administration of antiretroviral drugs, compared with oral, enhances delivery to lymphoid tissues in BALB/c mice.

Shetty Ravi Dyavar, Sushil Kumar, Nagsen Gautam, Anthony T Podany, Lee C Winchester, Jonathan A Weinhold, Timothy M Mykris, Palanisamy Nallasamy, Yazen Alnouti, Courtney V Fletcher

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 20 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Shetty Ravi DyavarAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Sushil KumarDepartment of Pharmaceutical Sciences, College of Pharmacy, UNMC, Omaha, NE, USA.
Nagsen GautamDepartment of Pharmaceutical Sciences, College of Pharmacy, UNMC, Omaha, NE, USA.
Anthony T PodanyAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Lee C WinchesterAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Jonathan A WeinholdAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Timothy M MykrisAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.
Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, College of Medicine, UNMC, Omaha, NE, 68198, USA.
Yazen AlnoutiDepartment of Pharmaceutical Sciences, College of Pharmacy, UNMC, Omaha, NE, USA.
Courtney V FletcherAntiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.ORCID 0000-0002-3703-7849
University of Nebraska Medical Center · US

Funding

Therapeutics Core (Page 286)P30MH062261 · NIMH · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI GENDELMAN, HOWARD E · 2000 to 2021
$37.7M
The Lymphoid Tissue Pharmacology of Antiretroviral DrugsR01AI124965 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI FLETCHER, COURTNEY V · 2016 to 2020
$3.7M
NIAID NIH HHS R01 AI124965NIAID NIH HHS R01-AI124965NIH HHS NIMH P30 MH062261NIMH NIH HHS P30 MH062261
6 · The paper itself

Abstract

backgroundMultiple tissue reservoirs are established soon after HIV infection, and some tissues may also be pharmacological sanctuaries. Parenteral administration of antiretroviral (ARV) drugs for treatment and prevention of HIV infection is an active area of drug development. The influence of route of administration on ARV tissue pharmacokinetics is not known.

objectivesTo investigate ARV pharmacokinetics in lymphatic and select non-lymphatic tissues (e.g. brain and testes) after intramuscular and subcutaneous administration compared with oral in BALB/c mice.

methodsTissue concentrations of cobicistat, efavirenz, elvitegravir, maraviroc, rilpivirine, tenofovir alafenamide and tenofovir disoproxil fumarate were determined. The tissue penetration ratio (TPR) was the primary measure for comparison; a change in TPR arises from factors affecting tissue distribution controlling for changes in systemic bioavailability.

resultsIntramuscular and subcutaneous delivery increased TPRs in the lymph node and spleen for 27 of 28 (96%) drug administration events. Decreased TPRs, however, were found in some tissues such as the brain and testes.

conclusionsThese results demonstrate a change in route of drug administration from oral to intramuscular or subcutaneous can change tissue uptake. This has implications for HIV pharmacotherapy. For example, HIV persists in lymphoid tissues despite long-term oral ARV therapy, and low ARV concentrations have been found in lymphoid tissues. The improved ARV lymphatic tissue bioavailability with intramuscular and subcutaneous administration allows future studies to investigate these routes of drug administration as a therapeutic manoeuvre to limit viral persistence and eliminate viral sanctuaries in the lymphatic tissues, which is a prerequisite for eradication of HIV.

Indexed as

Anti-HIV AgentsHIV InfectionsPharmaceutical PreparationsAnimalsLymphoid TissueMiceMice, Inbred BALB CAnti-HIV AgentsPharmaceutical Preparations

Identifiers

PMID34312680
PMCPMC8446911
OpenAlexW3185060353

What OpenQuestion holds

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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.