Pharmacokinetics of Amphotericin B Liposome for Infusion in Healthy Subjects Based on a Bioequivalence Study

Purpose:The aim of this study was to evaluate the pharmacokinetic characteristics and safety of Amphotericin B liposome for infusion in healthy volunteers based on a pilot bioequivalence clinical trial between a generic formulation and Ambisome.Methods: This single centre, randomized, single-dose, open-label, 2-way crossover bioequivalence study was conducted in healthy volunteers at the dose of 3 mg/kg.Blood samples were collected at pre-defined time points up to 1106 h after the start of the 2-h infusion.Plasma concentrations of free amphotericin B (liposome-unbound) and liposome-encapsulated amphotericin B were determined.Pharmacokinetic parameters were calculated using non-compartmental model.The formulations were considered bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratio of Cmax and AUCs of both products for free amphotericin B (liposome-unbound) and liposome-encapsulated amphotericin B were within 80.00%-125.00%for Ln-transformed data. Results and conclusion:Of the dosed 60 subjects, 56 subjects had completed the study.The generic liposomal amphotericin B for injection is bioequivalent to Ambisome in terms of the Pharmacokinetic parameters for free amphotericin B (liposome-unbound) and liposome-encapsulated amphotericin B