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 lipophili c drugs such as digoxin. Polysorbate 80 and Cremophor EL (polyoxyl 35 casto r oil) are such surfactants but they mag, also modulate the action of P-gly coprotein, an energy-dependent "counter-transport'' system implicated ill t he phenomenon of multidrug resistance in cancer cells. P-glycoprotein is al so present in the intestine on the apical membrane of mature enterocytes an d can potentially reduce the absorption of a wide range of drugs. In this s tudy, 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 produ cts could be shown with our in vitro model. Cremophor EL and Polysorbate 80 had no toxic effects at the concentrations used. These results suggest tha t surfactants such as Cremophor EL and Polysorbate 80 should not only suppo rt solubilization but can also modulate the P-glycoprotein system to improv e the bioavailability of poorly absorbed drugs.