Effect of surfactants on absorption through membranes III: effects of dioctyl sodium sulfosuccinate and poloxalene on absorption of a poorly absorbable drug, phenolsulfonphthalein, in rats.
The influence of dioctyl sodium sulfosuccinate and poloxalene on the GI absorption of phenolsulfonphthalein in the rat was studied. Urinary excretion data after oral administration of the drug to intact rats and loss of the drug from the whole small intestine as a loop were both utilized to assess the effect of the surfactants on absorption. Dioctyl sodium sulfosuccinate markedly increased the absorption of the drug, and the extent was dependent on the surfactant concentration. Maximum effect was observed at the reported ED50 in rats, of the surfactant as a fecal softener. The mechanism responsible for absorption enhancement seems to be an alteration of the permeability of the intestinal membrane. Micellar complexation between the drug and the surfactant resulted in a lesser increase in absorption at the higher surfactant concentrations. Poloxalene did not increase drug absorption, but higher concentrations caused a decrease in absorption due to micellar entrapments of the drug molecules. The influence of dioctyl sodium sulfosuccinate on the peritoneal absorption of the drug was also investigated. Lower doses of the surfactant increased absorption of the drug by altering the membrane permeability. Higher doses decreased absorption due to unavailability of the drug molecules entrapped in the micelles.
D000818:Animals; D004064:Digestive System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010537:Peritoneum / Q000187:drug effects; D010635:Phenolphthaleins / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000008:administration & dosage / Q000378:metabolism*; D011060:Poloxalene / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*
D010635:Phenolphthaleins; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D011060:Poloxalene; D010637:Phenolsulfonphthalein