Pharmacokinetic Equivalence of Amphosom^TM, a Newly Developed Liposomal Amphotericin B, to Ambisome^Ⓡ

Purpose: This study evaluated the bioequivalence of a newly developed liposomal amphotericin B (LAmB) formulation (DKF-5122, Amphosom™) relative to AmBisome^Ⓡ and mechanistically characterized the pharmacokinetic property. Methods: The two-period crossover trial included a patient cohort receiving once-daily infusions for 5 days per period and a healthy-adult cohort receiving a single dose per period. Both cohorts received 3 mg/kg intravenously, and plasma concentrations of LAmB and free drug (fAmB) were analyzed. Bioequivalence in healthy adults was evaluated using conventional criteria. A joint population model was developed based on healthy-adult data, linking LAmB and fAmB through first-order liposomal release and linear disposition. Model adequacy was assessed by goodness-of-fit diagnostics, prediction-corrected visual predictive checks, and bootstrap analysis. Results: Thirty-one participants contributed to the dataset (six patients and twenty-five healthy adults). In healthy adults, Test-to-Reference geometric mean ratios (90% confidence intervals) were 1.08 (1.04–1.12) for the maximum concentration of LAmB and 1.01 (0.94–1.08) for the area under the curve; for fAmB, the corresponding values were 1.00 (0.91–1.10) and 1.01 (0.95–1.07), meeting conventional bioequivalence criteria. Both LAmB and fAmB were well described by 3-compartment models, and the only formulation-related difference was a statistically significant reduction in the central compartment volume of LAmB for the Test formulation. However, this difference was not of a magnitude that would meaningfully affect the BE outcome. Covariate effects were not clinically relevant. Conclusions: Amphosom™ achieved pharmacokinetic bioequivalence to AmBisome^Ⓡ, and the joint model explained the observed similarity by quantifying liposomal release and systemic disposition of LAmB and fAmB. ClinicalTrials.gov identifier: NCT05749380.