Evidence map›Paper›PMID 30837282›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2019

Intranasal Coadministration of a Diazepam Prodrug with a Converting Enzyme Results in Rapid Absorption of Diazepam in Rats.

Davin Rautiola, Patricia D Maglalang, Narsihmulu Cheryala, Kathryn M Nelson, Gunda I Georg, Jared M Fine, Aleta L Svitak, Katherine A Faltesek, Leah R Hanson, Usha Mishra and 3 more

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

Article in The Journal of pharmacology and experimental therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-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

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. International journal of molecular sciences · 2025
    Article
  2. Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. A Curiously Linear Path to Academic Drug Discovery.ACS medicinal chemistry letters · 2020
    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

13 authors at 1 institution in 1 country.

Davin RautiolaDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0002-1472-2739
Patricia D MaglalangDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Narsihmulu CheryalaDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Kathryn M NelsonDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0001-8274-2064
Gunda I GeorgDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0002-8900-9460
Jared M FineDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0002-0271-9065
Aleta L SvitakDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Katherine A FaltesekDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Leah R HansonDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Usha MishraDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).
Lisa D ColesDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0003-3613-9904
James C CloydDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.).ORCID 0000-0002-3607-6619
Ronald A SiegelDepartments of Pharmaceutics (D.R., R.A.S.), Experimental and Clinical Pharmacology (J.C.C.), Medicinal Chemistry (N.C., K.M.N., G.I.G.), and Biomedical Engineering (R.A.S.), Center for Orphan Drug Research (P.D.M., U.M., L.D.C., J.C.C.), and Institute for Therapeutics Discovery and Development (N.C., K.M.N., G.I.G.), University of Minnesota, Minneapolis, Minnesota; and Neuroscience Research, HealthPartners Institute, St. Paul, Minnesota (J.M.F., A.L.S., K.A.F., L.R.H.) siege017@umn.edu.ORCID 0000-0002-9591-1282
United States Nuclear Regulatory Commission · US

Funding

MIN-REACH Research Evaluation and Commercialization HubU01HL127479 · NHLBI · UNIVERSITY OF MINNESOTA · PI GURVICH, VADIM J., HUBEL, ALLISON · 2015 to 2017
$3.0M
NHLBI NIH HHS U01 HL127479
6 · The paper itself

Abstract

Intranasal administration is an attractive route for systemic delivery of small, lipophilic drugs because they are rapidly absorbed through the nasal mucosa into systemic circulation. However, the low solubility of lipophilic drugs often precludes aqueous nasal spray formulations. A unique approach to circumvent solubility issues involves coadministration of a hydrophilic prodrug with an exogenous converting enzyme. This strategy not only addresses poor solubility but also leads to an increase in the chemical activity gradient driving drug absorption. Herein, we report plasma and brain concentrations in rats following coadministration of a hydrophilic diazepam prodrug, avizafone, with the converting enzyme

Indexed as

Administration, IntranasalAminopeptidasesAnimalsAnticonvulsantsBiological AvailabilityDiazepamDipeptidesDrug CompoundingMaleNasal CavityProdrugsRatsRats, Sprague-Dawleyaminopeptidase BAminopeptidasesAnticonvulsantsDiazepamDipeptidespro-diazepamProdrugs

Identifiers

PMID30837282
PMCPMC6806351
OpenAlexW2920593143

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.