The bioavailability (
BA
) of
E
3810, an unstable compound in acid, was studeid by controlling gastric pH in beagle dogs. The BAs, after the administration of
E
3810 solution orally to dogs with a low or a high gastric pH, were 3.16 ± 1.28% and 76.
4
± 13.8%, respectively. These results suggested that
E
3810 decomposes rapidly in the presence of gastric acid, but its
BA
is high if the decomposition of
E
3810 is avoided in the gastrointestinal tract. To establish a dosage form of
E
3810 for toxicity testing in the dog,
E
3810 enteric-coated tablets (ϕ=6.
5
mm) and
E
3810 solution were administered. The
tmax after the administration of
E
3810 enteric-coated tablets was prolonged (
tmax=
5
.42 hr), suggesting a slow gastric emptying, or a delay in the release of
E
3810. In contrast, when the tablets were asministered orally to fasted beagle dogs,
tmax was obtained within 1 hr, suggesting rapid release once the tablet left the stomach. After administration of
E
3810 solution to beagle dogs with a high gastric pH, the
BA
was high, with the lowest variability. In the preliminary toxicity test,
E
3810 solution was administered to dogs with a high gastric pH once a day for seven days. The plasma concentrations of
E
3810 on day 1 and day
7
increased dose-dependently, and there is no difference in pharmacokinetics between day 1 and day
7
. These results indicate that the method to control gastric pH in dogs is useful for the dosing of a compound that is unstable in gastric acid.
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