Amophotericin B lipid preparations in the lung

Weiler, S., Vogelsinger, H., Bellmann-Weiler, R., Joannidis, M., Bellmann, R.

Author address: 

Innsbruck Medical School, INNSBRUCK, Austria

Abstract: 

The three lipid formulations of amphotericin B (AMB), liposomal amphotericin B (LAMB, AmBisome), amphotericin B colloidal dispersion (ABCD, Amphocil; Amphotec) and amphotericin B lipid complex (ABLC, Abelcet), display striking differences in their pharmacokinetic behaviour in plasma. The aim of this study was to determine AMB concentrations in whole lung tissue, epithelial lining fluid (ELF) and pleural effusion after administration of AMB lipid preparations in order to investigate their target-site penetration. Whole lunge tissue concentrations of AMB were determined in autopsy material of 29 patients (LAMB: n=7, ABCD: n=13, ABLC: n=9). AMB levels in ELF were measured in bronchoalveolar lavage specimens of 30 (LAMB: n=6, ABCD: n=18, ABLC: n=6) and pleural effusion specimen of 7 (LAMB: n=1, ABCD: n=5, ABLC: n=1) critically ill patients, who were on treatment with lipid formulated AMB. The penetration ratio was calculated by comparing the concentrations in ELF and pleural effusion with simultaneous levels of lipid formulated AMB in plasma. The volume of ELF was calculated by the urea dilution method. Lipid-encapsulated and liberated AMB in plasma and pleural effusion were quantified separately via solid phase extraction in LAMB and ABCD treated patients. All samples were concentrated and purified by solid phase extraction. Subsequently AMB was quantified by high-performance liquid chromatography. Remarkable differences in the lung penetration of the three AMB lipid formulations were found. After treatment with ABCD and ABLC, mean concentrations in lung tissue were higher than after LAMB (ABCD: 32.62 µg/g, ABLC: 31.96 µg/g, LAMB: 11.63 µg/g). Mean concentrations in ELF were much lower compared to whole lung tissue. The highest concentrations in ELF, were observed after treatment with LAMB (1.86 µg/ml) and ABLC (1.86 µg/ml) in contrast to ABCD (0.33 µg/ml). The penetration ratio in ABLC and ABCD treatment was higher than in LAMB therapy. In pleural effusion, penetration ratios of total AMB amounted 4% in LAMB, 44% in ABLC and 16 ± 8% in ABCD therapy. Penetration ratios for the liberated AMB fraction were 8 and 18 ± 9% for LAMB and ABCD, respectively. The levels of AMB at target-site depend on the administered formulation and the cumulative doses. Further studies are required for clarifying the impact of these differences on clinical outcome.
2007

abstract No: 

P290

Full conference title: 

3rd Trends in Medical Mycology
    • TIMM 3rd (2011)