Work

Oral hyoscine butylbromide exerts spasmolytic effects in both gastrointestinal and urogenital tissues in rats

Year: 2025

Type: article

Abstract: 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.

Source: British Journal of Pharmacology

DOI: 10.1111/bph.17474

Authors: Sara Traserra, Terence Appelqvist, Robert Lange, Maura Corsetti, Marcel Jimenez