Evidence map›Paper›PMID 39198753›Full record

ArticleThe journal of headache and pain2024

Comparison of gepant effects at therapeutic plasma concentrations: connecting pharmacodynamics and pharmacokinetics.

Deirdre M Boucherie, Ruben Dammers, Arnaud Vincent, A H Jan Danser, Antoinette MaassenVanDenBrink

Abstract readComparative Study
In one paragraph

Article in The journal of headache and pain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. 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

5 authors.

Deirdre M BoucherieDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Ruben DammersDepartment of Neurosurgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Arnaud VincentDepartment of Neurosurgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
A H Jan DanserDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Antoinette MaassenVanDenBrinkDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands. a.vanharen-maassenvandenbrink@erasmusmc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOrally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance.

methodsWe examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research.

resultsWe showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations.

conclusionsThe relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

Indexed as

Administration, IntranasalCalcitonin Gene-Related PeptideMigraine DisordersAdultAzepinesCalcitonin Gene-Related Peptide Receptor AntagonistsFemaleHumansMaleMeningeal ArteriesMiddle AgedAzepinesCalcitonin Gene-Related PeptideCalcitonin Gene-Related Peptide Receptor AntagonistsAnti-CGRPAtogepantGepantMigraineRimegepantTrigeminalUbrogepantZavegepant

Identifiers

PMID39198753
PMCPMC11351853

What OpenQuestion holds

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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.