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.