Amphotericin B liposomal clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Clinical Pharmacology
Pharmacokinetics
The assay used to measure amphotericin B in the serum after administration of AmBisome does not distinguish amphotericin B that is complexed with the phospholipids of AmBisome from amphotericin B that is uncomplexed. The pharmacokinetic profile of amphotericin B after administration of AmBisome is based upon total serum concentrations of amphotericin B. The pharmacokinetic profile of amphotericin B was determined in febrile neutropenic cancer and bone marrow transplant patients who received 1-2 hour infusions of 1 to 5 mg/kg/day AmBisome for 3 to 20 days.
The pharmacokinetics of amphotericin B after administration of AmBisome is nonlinear such that there is a greater than proportional increase in serum concentrations with an increase in dose from 1 to 5 mg/kg/day. The pharmacokinetic parameters of total amphotericin B (mean ± SD) after the first dose and at steady state are shown in the table below.
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Distribution
Based on total amphotericin B concentrations measured within a dosing interval (24 hours) after administration of AmBisome, the mean half-life was 7-10 hours. However, based on total amphotericin B concentration measured up to 49 days after dosing of AmBisome, the mean half-life was 100-153 hours. The long terminal elimination half-life is probably a slow redistribution from tissues. Steady state concentrations were generally achieved within 4 days of dosing.
Although variable, mean trough concentrations of amphotericin B remained relatively constant with repeated administration of the same dose over the range of 1 to 5 mg/kg/day, indicating no significant drug accumulation in the serum.
Metabolism
The metabolic pathways of amphotericin B after administration of AmBisome are not known.
Excretion
The mean clearance at steady state was independent of dose. The excretion of amphotericin B after administration of AmBisome has not been studied.
Pharmacokinetics in Special Populations
Renal Impairment
The effect of renal impairment on the disposition of amphotericin B after administration of AmBisome has not been studied. However, AmBisome has been successfully administered to patients with pre-existing renal impairment (see DESCRIPTION OF CLINICAL STUDIES).
Hepatic Impairment
The effect of hepatic impairment on the disposition of amphotericin B after administration of AmBisome is not known.
Pediatric and Elderly Patients
The pharmacokinetics of amphotericin B after administration of AmBisome in pediatric and elderly patients has not been studied; however, AmBisome has been used in pediatric and elderly patients (see DESCRIPTION OF CLINICAL STUDIES).
Gender and Ethnicity
The effect of gender or ethnicity on the pharmacokinetics of amphotericin B after administration of AmBisome is not known.[1]
References
Adapted from the FDA Package Insert.