Importance of bile acids for novel oral absorption system containing polyamines to improve intestinal absorption.
The synergetic improving effect of bile acids with spermine (SPM), a major polyamine, on the absorption of rebamipide, a poorly soluble and poorly absorbable drug (BCS Class IV), was evaluated in rats and beagle dogs. Although the absorption of rebamipide was improved by the addition of polyamines alone in normal rats, it was not improved in bile duct ligated (BDL) rats. The combinatorial use of sodium taurocholate (STC), a bile acid, with SPM improved the absorption of rebamipide even in BDL rats. In the beagle dogs, the oral administration of SPM alone did not enhance the absorption of rebamipide, but the combinatorial use of STC with SPM improved the absorption as well as in the BDL rats. These results indicate that bile acids are indispensable for the novel formulation containing SPM to improve the absorption of rebamipide after oral administration.
Miyake
Masateru
M
Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co., Ltd., 224-18 Ebino, Hiraishi, Kawauchi-cho, Tokushima 771-0182, Japan.
Minami
Takanori
T
Toguchi
Hajime
H
Odomi
Masaaki
M
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001652:Bile Ducts / Q000502:physiology; D015317:Biogenic Polyamines / Q000494:pharmacology*; D004285:Dogs; D007408:Intestinal Absorption / Q000187:drug effects*; D008026:Ligation; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D015317:Biogenic Polyamines; D015363:Quinolones; D013096:Spermine; D013656:Taurocholic Acid; C052785:rebamipide; D000409:Alanine