Combinatorial use of sodium laurate with taurine or L-glutamine enhances colonic absorption of rebamipide, poorly absorbable antiulcer drug, without any serious histopathological mucosal damages.
We previously reported that the combinatorial use of sodium laurate (C12) with several amino acids such as taurine (Tau) and L-glutamine (L-Gln) enhanced the colonic absorption of phenol red with attenuating the local toxicity caused by C12. However, even these amino acids could not protect epithelial cells from being damaged if the mucosal damage got worse to the coagulation necrosis by an excessive dose of C12. Comparing C12 with sodium caprate (C10), used in drug products marketed, 100 micromol C10 was needed to exert the similar absorption-enhancement of rebamipide, a poorly absorbable antiulcer drug, to that by 10 micromol C12, and 100 micromol C10 was obviously more toxic to the mucosa than 10 micromol C12. The combinatorial use of C12 with Tau or L-Gln enhanced the colonic absorption of rebamipide four to nine times larger in AUC than the control. Histopathologic studies clearly showed that Tau and L-Gln exerted the cytoprotective action on epithelial cells suffering from slight damages such as shrinkage and exfoliation, more articulately at 6 h than at 1.5 h after dosing. In conclusion, the combinatorial use of C12 with Tau or L-Gln could lead to a novel formulation improving the bioavailability of poorly absorbable drugs without any serious local damages.
Miyake
Masateru
M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka Okayama 700-8530, Japan.
Oka
Yoshikazu
Y
Minami
Takanori
T
Toguchi
Hajime
H
Odomi
Masaaki
M
Ogawara
Ken-Ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000277:Adjuvants, Pharmaceutic / Q000009:adverse effects / Q000494:pharmacology*; D000284:Administration, Oral; D000409:Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000596:Amino Acids / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics; D001682:Biological Availability; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D005973:Glutamine / Q000009:adverse effects / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007850:Lauric Acids / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D015363:Quinolones / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000009:adverse effects / Q000494:pharmacology
D000277:Adjuvants, Pharmaceutic; D000596:Amino Acids; D000897:Anti-Ulcer Agents; D007850:Lauric Acids; D015363:Quinolones; D005973:Glutamine; C030358:lauric acid; D013654:Taurine; C052785:rebamipide; D000409:Alanine