Influence of antioxidants on the bioactivity of amphotericin B.

Four antioxidants, propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, and d-alpha-tocopherol acid succinate were found to stabilize amphotericin B and to prolong its antifungal activity against Candida albicans. Although each of the antioxidants was effective in this respect, propyl gallate and butylated hydroxyanisole were better than butylated hydroxytoluene and d-alpha-tocopherol acid succinate. None of the antioxidants alone adversely affected normal cell growth. It is suggested that amphotericin B instability is due, at least in part, to lability of the carbon-carbon double bonds of the polyene moiety toward autoxidation. By protecting the drug molecule with an antioxidant, it is possible to significantly lower the quantity of AB necessary to obtain particular antifungal effects.