The main absorption site of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]
propionate (AL-294) in rats was the upper portion of the small intestine. Both
AL-294 and
AL-294 acid (2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]
propionic acid), a hydrolyzed form of
AL-294, were absorbed in a smaller quantity under the bile
fistula condition (pancreatic juice and bile were excluded). Compared with the absorption of
AL-294 as an
emulsion under the
sham operation condition, the absorption of
AL-294 as the
emulsion decreased under the condition where only pancreatic juice was excluded. The bioavailability under this condition was very similar to that under the bile
fistula condition, whereas the absorption of
AL-294 acid did not decrease when the pancreatic juice was excluded. From these results, the absorption mechanism of
AL-294 is considered as follows:
AL-294 was hydrolyzed to
AL-294 acid by
lipase in pancreatic juice, then
AL-294 acid was solubilized with
bile salts to form mixed
micelles in the intestinal lumen.
AL-294 acid from this form was easily absorbed into the systemic circulation. Absorption of
AL-294 increased when the particle size of the
emulsion was smaller. The reason was assumed to be that the smaller particle size offered the greater oil-water interface for
lipase activity against
AL-294.