title: Effect of chitosan on gastrointestinal absorption of water-insoluble drugs following oral administration in rats.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Meijo University, Yagotoyama, Nagoya, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nadai
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tajiri
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshizumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Ying Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: Masao
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Tsunekawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D048271:Chitosan / Q000494:pharmacology*; D006118:Griseofulvin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D051381:Rats; D012995:Solubility
chemical_list: D006118:Griseofulvin; D048271:Chitosan; D007213:Indomethacin