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标题：Enhanced Rectal Absorption of Amphotericin B Lyophilized with Glycyrrhizinate in Rabbits
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作者：Makoto TANAKA ; Etsuhisa KUWAHARA ; Masahiro TAKAHASHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：8
页码：853-857
DOI：10.1248/bpb.21.853
出版社：The Pharmaceutical Society of Japan
摘要：The influence of bases and additives in the formulation for rectal absorption of amphotericin B (AMB) lyophilized with dipotassium glycyrrhizinate (GLYK) ws investigated using rabbits in relation to an in vitro release test. The release of AMB from the fatty base of Witepsol or a medium chain triglyceride (MCT) was markedly faster than that from the hydrophilic base of macrogol. The addition of polyoxyethylene (2) lauryl ether (POE(2)LE) into the fatty bases led to a marked increase in the release rate, wherease POE(9)LE or sodium lauryl sulfate resulted in a significantly lower release rate. Animals received rectally each of seven AMB formulatins of Witepsol H-15, macrogol, MCT with surfactants and aqueous solution. The absorption of the AMB lyophilized mixture with GLYK at a 1 : 9 molar ratio from a MCT base was significantly superior to that from macrogol. The addition of POE(2)LE into the MCT base resulted in a marked increase in bioavailability, showing the highest bioavailability of 4.9%. High serum levels of over 100 ng/ml of serum were maintained for 24 h following administration. The lowest bioavailability was 0.32% for the macrogol suppository. There was a good correlation between the release rate of AMB from the formulations and bioavailability. These results suggest that an AMB rectal formulation may provide a promising therapeutic alternative to infusion, taking into account the serum level of AMB exceeding the minimal inhibitory concentration of the infecting organism.
关键词：amphotericin B;dipotassium glycyrrhizinate;rectal absorption;suppository;drug release;surfactant