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KMID : 0369819970270010001
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Jorunal of Korean Pharmaceutical Sciences
1997 Volume.27 No. 1 p.1 ~ p.10
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Hepatic Uptake and Stability of Acyclovir - Asialofetuin Conjugate
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손성호/Son SH
허근/이영대/오두만/용철순/Huh K/Lee YD/Oh DM/Yong CS
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Abstract
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For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When [H3] acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at 37?C. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of 0.1?10μg/ml. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.
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KEYWORD
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Hepatic uptake, Asialofetuin, Acyclovir, Stability, Drug targeting
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