Effect of dodecylmaltoside (DDM) on uptake of BCS III compounds, tiludronate and cromolyn, in Caco-2 cells and rat intestine model.
The efficacy of n-lauryl-beta-D-maltopyranoside, (dodecylmaltoside, DDM) as a permeability-enhancer for tiludronate and cromolyn (BCS Class III, water-soluble compounds with oral bioavailability < 5%) was evaluated in Caco-2 cell monolayers and rat intestinal sacs. In Caco-2 cells samples were collected over a 5-h period and transepithelial resistance (TEER) was measured concurrently. In rat intestinal sacs, samples of the test compounds and marker (Lucifer Yellow) were collected over a 40 min period; accumulation in the serosal fluid and intestinal tissue was measured. At lower concentration DDM had no effect on cromolyn permeability and a marginal increase was observed at higher concentration. Tiludronate permeability in the presence of DDM showed greater enhancement as compared to cromolyn. At higher concentration DDM appeared to cause permanent damage to the cell monolayer (irreversible change in TEER). In the intestinal tissue, DDM caused increased tissue accumulation of test compounds. This indicated that transport was not restricted to the paracellular route and damage to the intestinal tissue could not be ruled out. Based on the results obtained in this study it can be concluded that at concentrations that are non-toxic DDM appears to have a limited use to improve the oral absorption of cromolyn and tiludronate.
407 Walker Building, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. deepali.d.deshmukh@gsk.com
Deepali D
DD
Deshmukh
Rakesh
R
Nagilla
William R
WR
Ravis
Guru V
GV
Betageri
D000465:Algorithms; D000818:Animals; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism; D004205:Cromolyn Sodium / Q000493:pharmacokinetics*; D003902:Detergents / Q000494:pharmacology*; D004164:Diphosphonates / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007546:Isoquinolines; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D050071:Bone Density Conservation Agents; D003902:Detergents; D004164:Diphosphonates; D005456:Fluorescent Dyes; D005960:Glucosides; D007546:Isoquinolines; C040358:dodecyl maltoside; C058651:tiludronic acid; C017475:lucifer yellow; D004205:Cromolyn Sodium