Intradermal substance P as a challenge agent in healthy individuals
Rattachement africain : nl, gb, in, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Pharmacological challenge models are deployed to evaluate drug effects during clinical development. Intradermal injection of Substance P (SP) neuropeptide, a potential challenge agent for investigating local mediators, is associated with wheal and flare response mediated by the MRGPRX2 receptor. Although dose‐dependent data on SP effects exist, full characterization and information on potential carryover effect after repeated challenge are lacking. This open‐label, two‐part, prospective enabling study of SP intradermal challenge in healthy participants aimed to understand and distinguish between wheal and flare responses following various SP doses. Part 1 included one challenge visit to determine optimum SP dose range for evaluation in part 2, which determined variability in 20 participants and used intradermal microdialysis (IDM) for SP‐challenged skin sampling. At 5, 15, 50, and 150 pmol doses, respectively, posterior median area under the curve (AUC; AUC0–2h) was 4090.4, 5881.2, 8846.8, and 9212.8 mm2/min, for wheal response, and 12020.9, 38154.3, 65470.6, and 67404.4 mm2/min for flare response (SP‐challenge visit 2). When the challenge was repeated ~2 weeks later, no carryover effect was observed. IDM histamine levels were relatively low, resulting in low confidence in the data to define temporal characteristics for histamine release following SP challenge. No safety concerns were identified using SP. Wheal and flare responses following intradermal SP challenge were dose‐dependent and different. The results indicate that this challenge model is fit‐for‐purpose in future first‐in‐human studies and further assessment of novel drugs targeting dermal inflammatory disease responses, such as chronic spontaneous urticaria, chronic inducible urticaria, and pseudo‐allergic reactions.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Intradermal substance P as a challenge agent in healthy individuals
- Date Crossref
- 07/08/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Leiden University Medical Center pays non établi dans la noticeOrganisme public
-
Centre for Human Drug Research pays non établi dans la noticeStructure de recherche
-
Age UK pays non établi dans la noticeOrganisation à but non lucratif
-
Erasmus MC pays non établi dans la noticeÉtablissement de santé
-
GlaxoSmithKline (India) pays non établi dans la noticeEntreprise
-
GlaxoSmithKline (United States) pays non établi dans la noticeEntreprise
-
These authors should be considered joint first authors pays non établi dans la noticeInstitution
-
GSK pays non établi dans la noticeInstitution
-
Department of Dermatology Erasmus Medical Center Rotterdam The Netherlands Department of Dermatology pays non établi dans la noticeÉtablissement de santé
-
Leiden Academic Centre for Drug Research Leiden The Netherlands pays non établi dans la noticeInstitution
-
RefLab ApS Copenhagen N Denmark pays non établi dans la noticeStructure de recherche
Leiden University Medical Center, Centre for Human Drug Research et Age UK, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.