Intestinal absorption of 5-fluorouracil and its alkylcarbamoyl derivatives in the rat small intestine.
The intestinal absorption of 5-fluorouracil (1) and its alkylcarbamoyl derivatives possessing various lipophilic pro-moieties including the butylcarbamoyl, hexylcarbamoyl, octylcarbamoyl, and nonylcarbamoyl groups, was investigated in the rat using both in situ and in vitro techniques. All compounds showed greater apparent partition coefficients and lipophilic indices (k') (by HPLC) and lower solubilities in water than 1. Although enhancement of uptake by the everted intestine in vitro was observed when the alkylcarbamoyl chain length was increased, the appearance of the prodrugs in the mesenteric vein in the in situ intestinal loop (complete venous collection) was decreased and sustained. The conversion of alkylcarbamoyl derivatives to 1 was noted in the absorption process.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000378:metabolism*; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D005472:Fluorouracil