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

Traserra, Sara; Appelqvist, Terence; Lange, Robert; Corsetti, Maura; Jimenez, Marcel

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, meaning its effect outside the GI tract has been questioned. This pharmacokinetic/pharmacodynamic (PK/PD) study, conducted using female rats, aims to cover this gap.

Experimental Approach: PK study: HBB and atropine (comparator) were administered PO and IV to rats, and concentrations in plasma, and colon, uterus and urinary bladder (CUB) were measured. PD study-1: Concentration–response (C-R) curves of HBB and atropine (10−9–10−4 M) were obtained for carbachol (CCH)-induced (10−5 M) pre-contracted CUB; PD study-2: CUB were pre-incubated with HBB and atropine at maximum concentrations (Cmax) from PK study, and CCH C-R 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 were collected at 0.5 h (IV) and 4 h (PO), and CCH C-R curves (10−9–10−4 M) were obtained.

Key Results: PO HBB showed higher Cmax in CUB (192.5, 3.70 and 1.85 ng∙g−1, respectively) than plasma (0.008 ng∙mL−1). HBB and atropine reduced (concentration dependently) CCH-induced contractions in CUB. PO HBB showed highest spasmolytic activity in colon (40%), followed by uterus (30%) and urinary bladder (10%).
Conclusion and Implications: This is the first comparative study investigating PO and IV HBB and atropine in GI and non-GI tissues. Despite low bioavailability, PO HBB accumulates and exerts spasmolytic effects outside the GI tract.

Citation

Traserra, S., Appelqvist, T., Lange, R., Corsetti, M., & Jimenez, M. (2025). Oral hyoscine butylbromide exerts spasmolytic effects in both gastrointestinal and urogenital tissues in rats. British Journal of Pharmacology, https://doi.org/10.1111/bph.17474

• Journal Article Type: Article
• Acceptance Date: Dec 17, 2024
• Online Publication Date: Feb 13, 2025
• Publication Date: Feb 13, 2025
• Deposit Date: Jan 9, 2025
• Publicly Available Date: Feb 14, 2026
• Journal: British Journal of Pharmacology
• Print ISSN: 0007-1188
• Electronic ISSN: 1476-5381
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/bph.17474
• Keywords: colon; PK/PD study; smooth muscle; urinary bladder; uterus
• Public URL: https://nottingham-repository.worktribe.com/output/43954608
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.17474?af=R
• Additional Information: Received: 2024-05-31; Accepted: 2024-12-17; Published: 2025-02-13