Study on colon-specific pectin/ethylcellulose film-coated 5-fluorouracil pellets in rats.
The purpose of the present study is to assess the biodistribution and pharmacokinetics of pectin/ethylcellulose film-coated and uncoated pellets containing 5-fluorouracil (5-FU) in rats. Both coated and uncoated pellets were orally administered to the rats at a dosage equivalent to 15mg/kg. 5-FU concentrations in different parts of the gastrointestinal (GI) tract and plasma were quantitatively analyzed using a high-performance liquid chromatography (HPLC) assay. 5-FU released from uncoated pellets mainly distributes in the upper GI tract, however, 5-FU released from coated pellets mainly distributes in the cecum and colon. In plasma, the observed mean C(max) from the coated pellets group (3.65+/-2.3microg/mL) was lower than that of the uncoated pellets group (23.54+/-2.9microg/mL). The AUC values obtained from the uncoated pellets and the coated pellets were 49.08+/-3.1 and 9.06+/-1.2microgh/mL, respectively. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer.
He
Wei
W
Department of Pharmaceutics, School of Pharmaceutical Science, Hebei Medical University, 361 ZhongShan East Road, ShiJiaZhuang 050017, People's Republic of China.
Du
Qing
Q
Cao
De-Ying
DY
Xiang
Bai
B
Fan
Li-Fang
LF
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002432:Cecum / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D010368:Pectins / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004343:Drug Implants; C013517:ethyl cellulose; D010368:Pectins; D002482:Cellulose; D005472:Fluorouracil