Oral hyoscine butylbromide exerts spasmolytic effects in both gastrointestinal and urogenital tissues in rats
Traserra, Sara (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Appelqvist, Terence (Sanofi)
Lange, Robert (Sanofi)
Corsetti, Maura (University of Nottingham Medical School)
Jiménez Farrerons, Marcel (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Data:	2025
Descripció:	16 pàg.
Resum:	Background and Purpose: Hyoscine butylbromide (HBB) has a low oral (PO) bioavailability. Further, limited data on its activity on non-gastrointestinal (GI) smooth muscle spasms after oral dosing are available, causing its effects beyond the GI tract to be questioned. This pharmacokinetic/pharmacodynamic (PK/PD) study, conducted using female rats, aimed to cover this gap. Experimental Approach: PK study: HBB and atropine (as a comparator agent) were administered PO and IV to rats, and concentrations in plasma and tissues (colon, uterus and urinary bladder; CUB) were measured. PD study 1: concentration-response curves of HBB and atropine (10-9-10-4 M) were obtained for carbachol-induced (10-5 M) pre-contracted tissues; PD study 2: CUB were pre-incubated with HBB and atropine at maximum concentrations (Cmax) from PK studies and carbachol concentration-response curves (10-9-10-4 M) were obtained; PD study 3: HBB and atropine were administered PO and IV to rats as for PK study, CUB tissues were collected at 0. 5 h (IV) and 4 h (PO), and carbachol concentration-response curves (10-9-10-4 M) obtained. Key Results: PO HBB showed higher Cmax in CUB tissues than in plasma. HBB and atropine reduced, concentration-dependently, carbachol-induced contractions in CUB tissues. PO HBB showed highest spasmolytic activity in colon (40%), followed by uterus (30%) and urinary bladder (10%). Conclusion and Implications: This is the first comparison of PO and IV HBB and atropine in GI and non-GI tissues. Despite low bioavailability, PO HBB accumulated and exerted spasmolytic effects in tissues beyond the GI tract.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Colon ; PK/PD study ; Smooth muscle ; Urinary bladder ; Uterus
Publicat a:	British Journal of Pharmacology, Vol. 182 Núm. 11 (2025) , p. 2487-2502, ISSN 1476-5381

DOI: 10.1111/bph.17474
PMID: 39947210

16 p, 2.0 MB

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