Amphotericin B liposomal clinical pharmacology: Difference between revisions
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==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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|[[File:Kinetcisambisome.JPG|600px|thumb]] | |||
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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.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = AMBISOME (AMPHOTERICIN B) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [ASTELLAS PHARMA US, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f7be6506-4d20-401e-a0ff-02ad7c33158a | publisher = | date = | accessdate = }}</ref> | |||
==References== | ==References== | ||
Revision as of 15:25, 5 January 2014
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.
 |
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.