Pharmacokinetics and tolerance of liposomal amphotericin B in patients

Amphotericin B incorporated into small unilamellar liposomes prepared from soya phosphatidylcholine and cholesterol in a molar ratio of 7:3 was administered to 12 patients with suspected or documented systemic fungal infection. Each patient received 0.1, 0.4 and 1.0 mg/kg dose of liposomal amphotericin B. Liposomal amphotericin B was well tolerated by these patients with no dose-limiting toxicity. Mild to moderate fever with rigors occurred in 3 patients after the higher doses. Peak plasma amphotericin B concentrations, measured by HPLC; were 0.747-1.429 mg/L and 24 h trough concentrations were 0.148-0.363 mg/L. The mean T1/2 beta of amphotericin B was 17.2 h with a mean volume of distribution of 2.285 L/kg. While these pharmacokinetic parameters obtained with this liposomal amphotericin B formulation are comparable to the values obtained after conventional amphotericin B therapy, they are strikingly different from values obtained by other workers using small unilamellar liposomes with either positive or negative charge. Yet in animal experiments the distribution of all formulations are comparable.