Preparation and evaluation of Eudragit gels. VIII. Rectal absorption of 5-fluorouracil from Eudispert hv gels in rats.
Rectal absorption of the hydrophilic 5-fluorouracil (5-FU) in rats was studied with Eudispert hv gels with or without fatty acids as the rectal bases. In the absence of fatty acids, absolute bioavailabilities of 5-FU for Eudispert hv hydrogel and xerogel preparations increased approximately 2.5 times compared with those of Witepsol H-15 and PEG 2000 suppositories. When n-capric acid or linolenic acid was used as an absorption enhancer, absolute bioavailabilities of 5-FU were, respectively, 25.5 and 30.9% for Witepsol H-15 and 64.4 and 66.1% for PEG 2000. Furthermore, the absolute bioavailabilities of 5-FU for Eudispert hv hydrogel with n-capric acid or linolenic acid were 95.6% and 81.7%. The addition of capric acid or linolenic acid to the hydrogel was a useful method for increasing 5-FU permeability through the rectal membranes. These results are consistent with the observation that the total amounts of 5-FU remaining in the lumenal contents of the rectum and that accumulated in the rectal tissue decreased in relation to the increase in the bioavailabilities. Thus, the Eudispert hv hydrogel containing 5-FU with capric acid may be a useful rectal preparation for increasing the maximum plasma level and improving the absolute bioavailability of 5-FU.
Umejima
H
H
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kikuchi
A
A
Kim
N S
NS
Uchida
T
T
Goto
S
S
D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005782:Gels; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D011109:Polymethacrylic Acids; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000378:metabolism; D013488:Suppositories
D000180:Acrylic Resins; D005227:Fatty Acids; D005782:Gels; D011109:Polymethacrylic Acids; D013488:Suppositories; C038300:methylmethacrylate-methacrylic acid copolymer; D005472:Fluorouracil