Increased stool water content, more alkaline stool pH, but no difference in body weight between vehicle and tenapanor treated mice.
Cftr+/+ and Cftr -/-mice were intragastrically gavaged with either vehicle (1X PBS, pH 6.0) or tenapanor (30mg kg-1) twice a day for 21 days in the absence of oral PEG-containing laxative (Figure 1a). Weight and stool water content was recorded daily. Body weight was slightly higher in the Cftr+/+ group due to a higher number of males (Figure 1b). It was stable during the treatment period during the 3week period in the Cftr+/+ group and slightly decreased in the Cftr-/- group (possibly due to the stress related to the gavage), but was not different between tenapanor- and vehicle-treated mice in either group (Figure 1c,d).
A significantly higher stool water content was observed in the tenapanor-treated Cftr+/+ andCftr-/- throughout the gavage period (Figure 1e,f). The vehicle treated Cftr-/- mice displayed a decrease of stool water content post removal of Oralav (Figure 1f). This was less prominent in theCftr+/+ mice (Figure1e). In a subset of mice, we also measured the stool pH before and 3 hours after gavage with tenapanor (Figure 1g), and found the pH to be significantly lower inCftr-/- compared toCftr+/+ mice, and to be significantly increased after tenapanor gavage.