Effectiveness and toxicity screening of various absorption enhancers in the large intestine: intestinal absorption of phenol red and protein and phospholipid release from the intestinal membrane.
The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers. DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.
Uchiyama
T
T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Yamamoto
A
A
Hatano
H
H
Fujita
T
T
Muranishi
S
S
D000818:Animals; D019540:Area Under Curve; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004396:Coloring Agents / Q000493:pharmacokinetics; D005079:Excipients / Q000494:pharmacology* / Q000633:toxicity*; D007408:Intestinal Absorption / Q000187:drug effects*; D007420:Intestine, Large / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004396:Coloring Agents; D005079:Excipients; D010743:Phospholipids; D011506:Proteins; D010637:Phenolsulfonphthalein