Effect of chitosan on gastrointestinal absorption of water-insoluble drugs following oral administration in rats.

Chitosan is widely used as a dietary weight-loss supplement in Japan. In the present study, we examined the effect of chitosan on the gastrointestinal absorption profiles of the water-insoluble drugs, indomethacin and griseofulvin, and the water-soluble drugs, acetaminophen and cephalexin, after oral administration in rats. Rats received oral administration of chitosan (5 mg/kg or 25 mg/kg) dissolved in 5% acetic acid or vehicle 15 min before oral administration of each drug. Chitosan at a dose of 25 mg/kg, but not 5 mg/kg, significantly decreased the plasma concentrations of indomethacin and griseofulvin after administration as a suspension with a significant delay of the time to reach maximum concentration compared to the corresponding control values (vehicle-pretreated rats). However, pretreatment of chitosan (25 mg/kg) did not change the pharmacokinetics of indomethacin administered as a solution. Further, the same dose of chitosan had no effect on the pharmacokinetics of acetaminophen. The gastrointestinal absorption profile of an amino-beta-lactam antibiotic, cephalexin, which is actively absorbed via carrier-mediated transport system, was also unchanged. The present findings at least suggest the possibility that chitosan at high dose reduces the gastrointestinal absorption of water-insoluble drugs such as indomethacin and griseofulvin, but not water-soluble drugs, by diminishing the surfactant-like effect of bile acids.