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.