Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro.
Surfactants are classically used to improve the solubilization of lipophilic drugs such as digoxin. Polysorbate 80 and Cremophor EL (polyoxyl 35 castor oil) are such surfactants but they may also modulate the action of P-glycoprotein, an energy-dependent "counter-transport" system implicated in the phenomenon of multidrug resistance in cancer cells. P-glycoprotein is also present in the intestine on the apical membrane of mature enterocytes and can potentially reduce the absorption of a wide range of drugs. In this study, using the improved everted gut sac method, the effects of Polysorbate 80, Cremophor EL and cyclosporin on the absorption of digoxin were studied. An increase in the uptake of digoxin in the presence of these three products could be shown with our in vitro model. Cremophor EL and Polysorbate 80 had no toxic effects at the concentrations used. These results suggest that surfactants such as Cremophor EL and Polysorbate 80 should not only support solubilization but can also modulate the P-glycoprotein system to improve the bioavailability of poorly absorbed drugs.
Cornaire
G
G
Laboratoire de Cinétique des Xénobiotiques, Faculté des Sciences Pharmaceutiques, Toulouse, France.
Woodley
J F
JF
Saivin
S
S
Legendre
J Y
JY
Decourt
S
S
Cloarec
A
A
Houin
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D016572:Cyclosporine / Q000493:pharmacokinetics; D004077:Digoxin / Q000493:pharmacokinetics*; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008823:Micelles; D011136:Polysorbates / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002316:Cardiotonic Agents; D008823:Micelles; D011136:Polysorbates; D013501:Surface-Active Agents; C000515:cremophor EL; D004077:Digoxin; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D005990:Glycerol