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KMID : 0370220030470050331
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Yakhak Hoeji
2003 Volume.47 No. 5 p.331 ~ p.338
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Synthesis and Biopharmaceutical Studies of Cefazolin Butyrolactone Ester, a Novel Prodrug of Cefazolin
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이진환/Lee JH
조행남/최준식/Cho HN/Choi JS
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Abstract
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A butyrolactone ester of cefazolin (CFZ-BTL) was synthesized by the esterification of cefazolin (CFZ) with a-bromo-γ-butyrolactone. The synthesis was confirmed by the spectro scopic analysis. The CFZ-BTL was more lipophilic than the CFZ when assessed by n-octanol/water partition coefficients at various pH. The CFZ-BTL itself did not show any anti-microbial activity in vitro, but after oral administration of CFZ-BTL to rabbits, exerted significant anti-microbial activity in serum samples when measured by the inhibion zone method in nutrient agar plates, due to conversion of CFZ-BTL to an active metabolite, probably CFZ, in the body. The CFZ-BTL was also converted into CFZ as confirmed by in vitro incubation study, with tissue homogenates (liver, blood and intestine) of rabbits. The liver showed the fastest conversion rate, probably via the hydrolysis mechanism. in vivo metabolism of CFZ-BTL to CFZ was also confirmed in vivo serum samples by HPLC. The oral bioavailability of CFZ-BTL in rabbits was 1.6-fold increased when compared to CFZ, resulting from followed by enhanced lipophilicity increased passive absorption in the intestine.
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KEYWORD
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