|
KMID : 0369819970270020125
|
|
Jorunal of Korean Pharmaceutical Sciences
1997 Volume.27 No. 2 p.125 ~ p.131
|
|
|
Synthesis and Biopharmaceutical Studies of Ceftezole Ethoxycarbonyloxyethyl Ester
|
|
박용채/Park YC
이진환/박재영/Lee JH/Park JY
|
|
|
Abstract
|
|
|
|
Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.
|
|
|
KEYWORD
|
|
|
Ceftezole ethoxycarbonyloxyethyl ester, Ceftezole, Prodrug, Partition coefficient, Hydrolysis, Microbiological activity, Bioavailability
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|