[Improvement of stability and bioavailability of 1-hexylcarbamoyl-5-fluorouracil (HCFU) by O-carboxymethyl-O-ethyl-beta- cyclodextrin].
The possible utility of O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) as a novel drug carrier was studied in vitro and in vivo, by using 1-hexylcarbamoyl-5-fluorouracil (HCFU) as a model drug. The chemical instability of HCFU in solution and solid state was improved by CME-beta-CyD complexation. The in vitro release of HCFU from the CME-beta-CyD complex was decelerated in acidic solution, while accelerated at neutral pH regions, showing a typical delayed-release pattern. This pattern was clearly reflected in the blood levels after the oral administration of the complex to dogs, increasing the bioavailability. The present results suggested that CME-beta-CyD is useful as a delayed-release-type carrier for the oral administration of chemically labile HCFU.
Horiuchi
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Hirayama
F
F
Uekama
K
K
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004285:Dogs; D004337:Drug Carriers; D004355:Drug Stability; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008297:Male; D012995:Solubility; D047392:beta-Cyclodextrins
D000970:Antineoplastic Agents; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C062590:O-carboxymethyl-O-ethyl-beta-cyclodextrin; D047392:beta-Cyclodextrins; C017367:carmofur; D005472:Fluorouracil