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.