Development of an Oral Amphotericin B Formulation as an Alternative Approach to Parenteral Amphotericin B Administration in the Treatment of Blood-Borne Fungal Infections

Abstract

: In the Fall of 1999, we presented at medical “Grand Rounds” to a number of Infectious Diseases physicians at Vancouver General Hospital about the co-administration of several antifungal compounds in the treatment of blood-borne fungal infections to patients who were immunocompromised (i.e. cancer patients, patients waiting organ transplantation, HIV/AIDs patients, etc.). During the presentation, a physician from the back of the room called out “can you develop an oral formulation of amphotericin B which could be effective and not have the side-effects associated with the parenteral formulations of the drug”. The physician stated that an oral formulation would be a big step forward, improving patient compliance, helping in pre-treatment without admitting patients to the hospital prior to organ transplantation and it would be cost-effective. Initially, I responded to the physician, that it would not be possible to develop an oral amphotericin B formulation that could be absorbed from the gastrointestinal (GI) tract in a high enough concentration to be effective in treating blood-borne fungal infections and yet remains non-toxic due to the physical chemical properties of the drug. However, as I travelled back to my lab from the meeting, it struck me that our understanding of how lipids had been processed and orally absorbed from the GI had advanced to the point the maybe incorporating amphotericin B into such lipids might work. Within several years, our laboratory was able to develop a novel oral amphotericin B formulation that was indeed effective in treating systemic fungal infections without the side-effects associated with the drug in a variety of fungal animal models.