Application of DDS for Infectious Diseases: Liposomal Amphotericin B

Kaneko Yukihiro

doi:10.2745/dds.33.33

According to the autopsy report, the most frequent mycoses in Japan are aspergillosis, then candidiasis, cryptococcosis, followed by mucormycosis. On the other hand, the antifungal drugs that can be used in Japan are amphotericin B (AMPH-B) and liposomal amphotericin B (L-AMB), fluconazole, fosfluconazole, miconazole, itraconazole, voriconazole, micafungin, caspofungin and flucytosine. L-AMB is the first liposomal preparation as a pharmaceutical drug and it is a pioneer as a DDS of antifungal drugs. Although AMPH-B is a highly reliable antifungal agent with a wide antifungal spectrum, the conventional formulation has severe adverse effects such as hypokalemia and renal dysfunction. The main purpose in developing lipid formulations was to reduce side effects while maintaining high antifungal activity as AMPH-B. In fact it is more tolerable than its conventional formulation and it fulfilled the purpose of DDS. Ten years have passed since the start of clinical use, but L-AMB still remains to be recognized as one of the important drugs against fungal diseases in the various guidelines and clinical practice. Development of DDS for antifungal drugs is still less developed. Azoles and echinocandins have few side effects, and it may be one of the reasons that it is difficult to set clear purpose of DDS like L-AMB. Echinocandins exhibit fungicidal action against Candida spp. and are expected to be effective even in neutropenia. However, tissue penetration is poor as compared with azoles that have a fungistatic effect on Candida spp. Therefore, it is desirable to develop DDS for improving pharmacokinetics rather than reducing adverse effects.

Application of DDS for Infectious Diseases: Liposomal Amphotericin B

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