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

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.

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 (C_max) 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.

PO HBB showed higher C_max 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%).

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.