Abstract
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 μmol C10 was needed to exert the similar absorption-enhancement of rebamipide, a poorly absorbable antiulcer drug, to that by 10 μmol C12, and 100 μmol C10 was obviously more toxic to the mucosa than 10 μmol 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.
| Original language | English |
|---|---|
| Pages (from-to) | 911-921 |
| Number of pages | 11 |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 92 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2003 |
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Keywords
- Absorption enhancer
- Cytoprotection
- Histopathology
- L-glutamine
- Local toxicity
- Sodium laurate
- Taurine
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Chemistry(all)
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
Cite this
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. / Miyake, Masateru; Oka, Yoshikazu; Minami, Takanori; Toguchi, Hajime; Odomi, Masaaki; Ogawara, Ken Ichi; Higaki, Kazutaka; Kimura, Toshikiro.
In: Journal of Pharmaceutical Sciences, Vol. 92, No. 4, 01.04.2003, p. 911-921.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Miyake, Masateru
AU - Oka, Yoshikazu
AU - Minami, Takanori
AU - Toguchi, Hajime
AU - Odomi, Masaaki
AU - Ogawara, Ken Ichi
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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 μmol C10 was needed to exert the similar absorption-enhancement of rebamipide, a poorly absorbable antiulcer drug, to that by 10 μmol C12, and 100 μmol C10 was obviously more toxic to the mucosa than 10 μmol 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.
AB - 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 μmol C10 was needed to exert the similar absorption-enhancement of rebamipide, a poorly absorbable antiulcer drug, to that by 10 μmol C12, and 100 μmol C10 was obviously more toxic to the mucosa than 10 μmol 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.
KW - Absorption enhancer
KW - Cytoprotection
KW - Histopathology
KW - L-glutamine
KW - Local toxicity
KW - Sodium laurate
KW - Taurine
UR - http://www.scopus.com/inward/record.url?scp=0037381429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037381429&partnerID=8YFLogxK
U2 - 10.1002/jps.10362
DO - 10.1002/jps.10362
M3 - Article
C2 - 12661076
AN - SCOPUS:0037381429
VL - 92
SP - 911
EP - 921
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 4
ER -