Accelerated GI transit time upon treatment with Tenapanor
Gastrointestinal transit time (GTT) is prolonged in CF patients and in CFTR deficient mice (De Lisle, 2007; Dellschaft et al., 2021; Malagelada et al., 2020; Vitko et al., 2016). We therefore measured GTT after oral gavage of 30 mgkg-1 tenapanor or vehicle once per week. Compared to Cftr+/+ , theCftr-/- mice in the vehicle treated group showed a significantly longer transit time (Figure 2a,c). Upon treatment with Tenapanor, a significant decrease of transit time was observed from week 1 onwards in the Cftr-/- mice and in week 3 in the Cftr+/+ mice (Figure 2a,c). This reduction of GTT in both vehicle treated and tenapanor treatedCftr+/+ and Cftr-/-mice from week 1 to week 3 was independent of the effect of tenapanor on the stool water content in the 5 hours during the determination of GTT which showed a significant difference between vehicle and tenapanor treated mice of both genotypes (Figure 2b,d). Interestingly, a difference in the pre-gavage (0h) stool water content (not significant until week 2, but significant in week 3) between the vehicle and tenapanor treated Cftr+/+ mice but not in theCftr-/- mice was observed (which would be a time point of approx. 11 hours after their last gavage). This may indicate a different durability of tenapanor action inCftr+/+ and Cftr-/-intestine.