Amphotericin B Lipid Complex (Abelcet®) in the treatment of invasive mycoses: the North American experience

Abstract

Abelcet®, or Amphotericin B Lipid Complex, is a unique formulation, comprising an equimolar mixture of amphotericin B complexed with two lipids. In preclinical studies, Abelcet® was clearly demonstrated to be less toxic than amphotericin B desoxycholate and to be effective in models where amphotericin B was ineffective at its maximum tolerated dose. Pharmacokinetic studies in animals also showed that the concentration of Abelcet® in blood is similar or reduced compared to levels seen with conventional amphotericin B, with accumulation in the liver, lungs and spleen. Phase I clinical trials determined the optimum tolerated dose of Abelcet® to be 5 mg/kg d^-1. Data are now available for 228 cases (including 51 paediatric cases) of invasive fungal infection treated with Abelcet® in an open-label emergency-release protocol. All patients had to have failed on previous amphotericin B or other conventional antifungals, or to have unacceptable toxicity on amphotericin B, or underlying renal disease, or nephrotoxicity due to other drugs. Abelcet® was administered at a dose of 5 mg/kg d^-1 for 4 wk. Approximately one-third of patients had candidiasis, one-third aspergillosis and one-third other infections, including fusariosis. Of 183 cases evaluable for response, 126 (69%) had a clinical response (cure or improvement) which was mycologically confirmed in 55% (61/110 tested). Results in paediatric cases were similar to or better than those seen in the group as a whole. When comparisons were made between cases with different types of infection, underlying disease/immunosuppressive disorder, and degree of neutropenia, the response rates were very consistent from group to group. Treatment with Abelcet® was well tolerated and mean serum creatinine levels actually declined during therapy, particularly in patients with pre-existing renal dysfunction.