Investigation on physicochemical and biological differences of cefpodoxime proxetil enantiomers
Investigation on physicochemical and biological differences of cefpodoxime proxetil enantiomers
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DOI：
10.1016/j.ejpb.2006.05.001
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发表时间：
2006-10-01
影响因子：
4.9
通讯作者：
Bansal, Arvind K.
中科院分区：
文献类型：
--
作者：
Kakumanu, Vasu Kumar;Arora, Vinod;Bansal, Arvind K.
头孢泊肟酯(CP)是头孢泊肟酸(CA)的前体药物，以R-和S-对映体的外消旋混合物形式提供。CP只有50%的绝对生物利用度，导致生物利用度低的原因仍然知之甚少。本工作确定了CP的各个异构体的物理、化学和生物学性质，并探索了它们优化CP输送的能力。两种异构体表现出相似的pH稳定性行为，但R-异构体比S-异构体更容易受到酶代谢的影响，与从GIT不同片段收集的酶孵育时。根据体外和体内实验结果，使用S-异构体开发的剂型，如胃保留剂型，可以提高CP的口服生物利用度。(C)2006爱思唯尔B.V.保留所有权利。
Cefpodoxime proxetil (CP) is a prodrug of cefpodoxime acid (CA), and is supplied as racemic mixture of R- and S-enantiomers. CP has only 50% absolute bioavailability, and the reasons responsible for low bioavailability remain poorly understood. The present work ascertains physicochemical and biological properties of individual isomers of CP and explores their capacity to optimize delivery of CP. Both isomers showed similar pH stability behavior, but R-isomer was more susceptible to enzymatic metabolism compared to S-isomer, when incubated with enzymes collected from various segments of GIT. Based on the in vitro and in vivo results, use of S-isomer for development of a dosage form such as gastro-retentive dosage form can improve oral bioavailability of CP. (c) 2006 Elsevier B.V. All rights reserved.