The safety and efficacy of amphotericin B colloidal dispersion in the treatment of invasive mycoses.
Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1:1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity: the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.
Oppenheim
B A
BA
Withington Hospital, Manchester, United Kingdom.
Herbrecht
R
R
Kusne
S
S
D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D003102:Colloids; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects; D008297:Male; D009181:Mycoses / Q000188:drug therapy*; D012449:Safety
D003102:Colloids; D000666:Amphotericin B; D003404:Creatinine