Because of its broad spectrum, the polyene amphotericin B (AMB) has still an important role in treatment of invasive fungal infections. It is eliminated unchanged via the bile and the urine. However, its use is limited by infusion related adverse events and by its nephro-toxicity. Three less toxic lipid formulations are available, displaying different composition of their lipid moieties and thus different particle size and shape. Liposomal AMB (LAMB) comprises small uni-laminar vesicles. Its volume of distributions is small, its half-life is short and high plasma concentrations are achieved. AMB lipid complex (ABLC) forms large ribbon-like structures resulting in a large volume of distribution a half-life of about 1 week whereas only low plasma level are reached. The 3rd lipid formulation, AMB colloidal dispersion (ABCD) displays intermediate plasma levels, half-life and volume of distribution. Methods: AMB pharmacokinetics was analyzed in 18 critically ill patients on treatment with lipid-formulated AMB (13 requiring hemofiltration). Lipid-associated and liberated AMB were separated by solid phase extraction and quantified by high performance liquid chromatography. AMB tissue distribution was assessed in autopsy sample obtained from 32 patients who had died during therapy with lipid formulated AMB. Results: In critically patients, mean peak plasma levels (Cmax) of liberated AMB amounted to 0.5 ?g/ml after infusion of LAMB or ABCD, whereas Cmax of total AMB was 3.4 ?g/ml and 0.8 ?g after ABCD. The clearance (CL) of liberated AMB was 0.2 l/kg/h (CL of LAMB [lipid-formulated] = 0.08 l/kg/h, CL of ABCD = 3.0 l/kg/h). AMB-pharmacokinetics on and off hemofiltration were similar. Tissue concentrations of 100 ?g/g were reached in the liver, 70?g/g in the spleen. Lung concentrations were significantly higher after ABCD than after LAMB treatment (33 vs.12 ?g/g). Levels in myocardium and brain were 3 ?g/g and 1 ?g/g, respectively. Conclusions: 1) The lipid-associated moieties of AMB lipid formulations display considerable differences in their pharmacokinetics whereas pharmacokinetics of the liberated AMB fraction is independent from the preparation administered. 2) No dose adjustment is required during hemofiltration. 3) AMB accumulates in liver and spleen, tissue concentrations in lung and kidneys are intermediate and low in myocardium and brain.

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