Changes in intestinal absorption of 5-fluorouracil-treated rats.
5-Fluorouracil chemotherapy is often accompanied by gastrointestinal toxicity. In this study, we investigated the effect of 5-fluorouracil on the epithelial barrier function of rat small intestine by examining the absorption of a poorly absorbable marker, fluorescein isothiocyanate-labelled dextran (molecular weight 4,400). We further evaluated the intestinal absorption of 5-fluorouracil in rats treated orally with 5-fluorouracil once daily for 4 days. The small intestinal absorption of fluorescein isothiocyanate-labelled dextran and 5-fluorouracil was tested using in situ closed loop intestine technique and in vitro everted intestine technique, respectively. After administration of 5-fluorouracil to rats for 4 days, the body weight of rats decreased significantly and the fluorescein isothiocyanate-labelled dextran concentration in plasma increased significantly, compared with that of control rats to which the saline solution alone was administered. Moreover, the intestinal absorption of 5-fluorouracil in the 5-fluorouracil-treated rats was enhanced significantly, compared with that of control rats. The administration of 5-fluorouracil to rats caused body weight loss and epithelial barrier dysfunction of the small intestine in rats as shown by the increased permeation of the high molecular weight compound, fluorescein isothiocyanate-labelled dextran. The increased absorption of 5-fluorouracil after this treatment suggest that the 5-fluorouracil toxicity might be amplified by its treatment.
Hirata
K
K
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Horie
T
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D005472:Fluorouracil