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Effects of physiological factors on the bioavailability of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate in an emulsion in rats.

Abstract
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.
AuthorsH Toguchi, Y Ogawa, K Iga, T Shimamoto
JournalChemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 38 Issue 10 Pg. 2801-4 (Oct 1990) ISSN: 0009-2363 [Print] Japan
PMID2076566 (Publication Type: Journal Article)
Chemical References
  • Emulsions
  • Hypolipidemic Agents
  • AL 294
  • Clofibrate
Topics
  • Animals
  • Biological Availability
  • Clofibrate (administration & dosage, analogs & derivatives, pharmacokinetics)
  • Emulsions
  • Hypolipidemic Agents (administration & dosage, pharmacokinetics)
  • Intestinal Absorption
  • Male
  • Rats
  • Rats, Inbred Strains

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