Amphotericin B colloidal dispersion: an improved antifungal therapy

Abstract

Amphotericin B colloidal dispersion (ABCD) is a near 1:1 discoidal complex of amphotericin B (AMB) and sodium cholesteryl sulfate (SCS) arranged as a bilayer of SCS interspersed with AMB via noncovalent interactions. The complex is stable in blood and plasma with minimal dissociation. In vitro and in vivo studies show that ABCD is as effective and four to five times safer than conventional AMB (CAB) for fungal infection. Compared with CAB treatment, ABCD demonstrates reduced peak plasma levels, prolonged residence time, and lowered AMB levels in most tissues including kidney, the major target of toxicity for CAB. In 572 patients with systemic fungal infections secondary to severe underlying disease, ABCD doses ≤6 mg/kg/day were well tolerated, even in those who failed to tolerate or respond to CAB. Mild-to-moderate, dose-dependent, infusion-related adverse events typically seen with CAB were also observed with ABCD, with no sign of renal or hepatic toxicity. Complete or partial recovery was seen in 57.3%. Therefore, ABCD should be considered as an alternative treatment of systemic fungal infections.