Evidence map›Paper›PMID 27574509›Full record

ArticleFrontiers in pharmacology2016

Alcohol and Aldehyde Dehydrogenases Contribute to Sex-Related Differences in Clearance of Zolpidem in Rats.

Cody J Peer, Jonathan D Strope, Shaunna Beedie, Ariel M Ley, Alesia Holly, Karim Calis, Ronald Farkas, Jagan Parepally, Angela Men, Emmanuel O Fadiran and 4 more

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

Article in Frontiers in pharmacology, 2016. 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
1.5field-weighted citation impact, top 18% 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, 11 citations in OpenAlex.

  1. Article
  2. Age differences in brain structural and metabolic responses to binge ethanol exposure in fisher 344 rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Article
  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

14 authors at 5 institutions in 1 country.

Cody J PeerClinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Jonathan D StropeMolecular Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Shaunna BeedieMolecular Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Ariel M LeyMolecular Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Alesia HollyMolecular Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Karim CalisOffice of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring MD, USA.
Ronald FarkasOffice of New Drugs, Division of Neurology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring MD, USA.
Jagan ParepallyOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring MD, USA.
Angela MenOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring MD, USA.
Emmanuel O FadiranOffice of Women's Health, Office of the Commissioner, Food and Drug Administration, Silver Spring MD, USA.
Pamela ScottOffice of Women's Health, Office of the Commissioner, Food and Drug Administration, Silver Spring MD, USA.
Marjorie JenkinsOffice of Women's Health, Office of the Commissioner, Food and Drug Administration, Silver Spring MD, USA.
William H TheodoreClinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda MD, USA.
Tristan M SissungClinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
Center for Drug Evaluation and Research · USNational Institutes of Health · USUnited States Food and Drug Administration · USNational Cancer Institute · USNational Institute of Neurological Disorders and Stroke · US

Funding

Physiologic And Pharmacologic Studies In EpilepsyZIANS002236 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI THEODORE, WILLIAM · 2009 to 2020
$14.2M
6 · The paper itself

Abstract

objectivesThe recommended zolpidem starting dose was lowered in females (5 mg vs. 10 mg) since side effects were more frequent and severe than those of males; the mechanism underlying sex differences in pharmacokinetics (PK) is unknown. We hypothesized that such differences were caused by known sex-related variability in alcohol dehydrogenase (ADH) expression.

methodsMale, female, and castrated male rats were administered 2.6 mg/kg zolpidem, ± disulfiram (ADH/ALDH pathway inhibitor) to compare PK changes induced by sex and gonadal hormones. PK analyses were conducted in rat plasma and rat brain. KEY

findingsSex differences in PK were evident: females had a higher C MAX (112.4 vs. 68.1 ug/L) and AUC (537.8 vs. 231.8 h(∗)ug/L) than uncastrated males. Castration induced an earlier T MAX (0.25 vs. 1 h), greater C MAX (109.1 vs. 68.1 ug/L), and a corresponding AUC increase (339.7 vs. 231.8 h(∗)ug/L). Administration of disulfiram caused more drastic C MAX and T MAX changes in male vs. female rats that mirrored the effects of castration on first-pass metabolism, suggesting that the observed PK differences may be caused by ADH/ALDH expression. Brain concentrations paralleled plasma concentrations.

conclusionThese findings indicate that sex differences in zolpidem PK are influenced by variation in the expression of ADH/ALDH due to gonadal androgens.

Indexed as

drug metabolismpharmacokineticstestosteronezolpidem

Identifiers

PMID27574509
PMCPMC4983555
OpenAlexW2511828599

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.