Abstract
The development of a safe and efficacious drug involves a balance between bioavailability, toxicity and disposition within the body. If the drug is hydrophobic or acid labile, oral administration may lead to poor systemic exposure, necessitating a parenteral treatment regime. Amphotericin B (AmpB) is one example of a well established, highly efficacious drug that has a 50 year history of intravenous therapy. AmpB formulated as a micellar dispersion (Fungizone®; FZ) for IV use, remains one of the most effective agents in the treatment of systemic fungal infections, yet no oral formulations are currently commercially available. Recently, our laboratory has developed new oral lipid-based AmpB formulations with enhanced gastrointestinal (GI) tract absorption and antifungal activity with minimum renal toxicity. This review article will discuss these findings and present data to support two potential mechanisms for the enhanced GI tract absorption of AmpB when formulated in this oral lipid-based delivery system, namely an increase in lymphatic drug transport and a decrease in pre-systemic transporter-mediated drug efflux.
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