Pulmonary epithelial lining fluid concentrations after use of systemic amphotericin B lipid formulations

Area of Science:

• Pharmacology
• Critical Care Medicine
• Pulmonary Medicine

Background:

• Amphotericin B (AMB) is a critical antifungal agent.
• Different formulations of AMB exist, including liposomal AMB (LAMB), AMB colloidal dispersion (ABCD), and AMB lipid complex (ABLC).
• Understanding drug concentrations in specific body compartments, like pulmonary epithelial lining fluid (ELF), is crucial for optimizing treatment efficacy in critically ill patients.

Purpose of the Study:

• To quantify and compare Amphotericin B concentrations in the pulmonary epithelial lining fluid (ELF) of critically ill patients receiving different AMB formulations.
• To assess potential differences in drug distribution among LAMB, ABCD, and ABLC in the ELF.

Main Methods:

• Pulmonary epithelial lining fluid (ELF) samples were collected from 44 critically ill patients.
• Patients were treated with one of three AMB formulations: LAMB (n=11), ABCD (n=28), or ABLC (n=5).
• AMB concentrations in ELF were measured using standardized assays.

Main Results:

• Mean AMB concentrations in ELF were 1.60 ± 0.58 µg/ml for LAMB, 0.38 ± 0.07 µg/ml for ABCD, and 1.29 ± 0.71 µg/ml for ABLC.
• Despite observed differences, the variations in mean AMB levels across the three formulations in ELF were not statistically significant.
• This suggests comparable distribution into the ELF for these AMB formulations in this patient cohort.

Conclusions:

• The study determined AMB concentrations in ELF across different formulations in critically ill patients.
• While LAMB and ABLC showed numerically higher ELF concentrations than ABCD, these differences were not statistically significant.
• Further research may be needed to explore clinical implications and optimal dosing strategies for each AMB formulation in severe infections.