Oral Hyoscine butylbromide exerts spasmolytic effects both in gastrointestinal and urogenital tissues

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. (in press). Oral Hyoscine butylbromide exerts spasmolytic effects both in gastrointestinal and urogenital tissues. British Journal of Pharmacology, 1-40

• Journal Article Type: Article
• Acceptance Date: Dec 17, 2024
• Deposit Date: Dec 18, 2024
• Print ISSN: 0007-1188
• Electronic ISSN: 1476-5381
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Pages: 1-40
• Keywords: PK/PD study; smooth muscle; colon; urinary bladder; uterus.
• Public URL: https://nottingham-repository.worktribe.com/output/43095148
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/journal/14765381