Gastro-intestinal absorption of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate from different dosage forms in rats and dogs.
To obtain information as to a suitable formulation of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)-phenyl]propionate (AL-294), an antihyperlipidemic drug of low water solubility, the bioavailability after its oral administration in various dosage forms was evaluated in rats and dogs. After AL-294 was administered orally, AL-294 acid (2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionic acid), which is a metabolite of AL-294, was detected in the plasma. Therefore, absorbability of AL-294 was evaluated using plasma AL-294 acid levels. AL-294 in an oil solution or in a gelatin capsule showed poor absorption, whereas it's absorption was greatly enhanced in the form of an emulsion. The postprandial administration also showed better absorption. The elimination rate of AL-294 acid from the plasma after oral administration of the emulsion was similar to that after intravenous administration of a sodium salt of AL-294 acid.
Toguchi
H
H
Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Ogawa
Y
Y
Iga
K
K
Yashiki
T
T
Shimamoto
T
T
D000818:Animals; D002994:Clofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004285:Dogs; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000960:Hypolipidemic Agents; C067636:AL 294; D002994:Clofibrate