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

Abelcet, or Amphotericin B lipid Complex, is 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.