Amphotericin B lipid complex clinical pharmacology: Difference between revisions

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==Clinical Pharmacology==


<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  | title = ABELCET (AMPHOTERICIN B, DIMYRISTOYLPHOSPHATIDYLCHOLINE, DL- AND DIMYRISTOYLPHOSPHATIDYLGLYCEROL, DL-) INJECTION [SIGMA-TAU PHARMACEUTICALS, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5587db37-f21a-4a39-a319-e1077032ced9 | publisher =  | date =  | accessdate =  }}</ref>
===Pharmacokinetics===
 
The assay used to measure amphotericin B in the blood after the administration of ABELCET® does not distinguish amphotericin B that is complexed with the phospholipids of ABELCET® from amphotericin B that is uncomplexed.
 
The pharmacokinetics of amphotericin B after the administration of ABELCET® are nonlinear. Volume of distribution and clearance from blood increase with increasing dose of ABELCET®, resulting in less than proportional increases in blood concentrations of amphotericin B over a dose range of 0.6-5 mg/kg/day. The pharmacokinetics of amphotericin B in whole blood after the administration of ABELCET® and amphotericin B desoxycholate are:
 
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The large volume of distribution and high clearance from blood of amphotericin B after the admistration of ABELCET® probably reflect uptake by tissues. The long terminal elimination half-life probably reflects a slow redistribution from tissues. Although amphotericin B is excreted slowly, there is little accumulation in the blood after repeated dosing. AUC of amphotericin B increased approximately 34% from day 1 after the administration of ABELCET® 5 mg/kg/day for 7 days. The effect of gender or ethnicity on the pharmacokinetics of ABELCET® has not been studied.
 
Tissue concentrations of amphotericin B have been obtained at autopsy from one heart transplant patient who received three doses of ABELCET® at 5.3 mg/kg/day:
 
{|
|[[File:Kinetics2Abelcet.JPG|600px|thumb]]
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This pattern of distribution is consistent with that observed in preclinical studies in dogs in which greatest concentrations of amphotericin B after ABELCET® administration were observed in the liver, spleen, and lung; however, the relationship of tissue concentrations of amphotericin B to its biological activity when administered as ABELCET® is unknown.
 
====Special Populations====
 
'''Hepatic Impairment:''' The effect of hepatic impairment on the disposition of ABELCET® is not known.
 
'''Renal Impairment:''' The effect of renal impairment on the disposition of ABELCET® is not known. The effect of dialysis on the elimination of ABELCET® has not been studied; however, amphotericin B is not removed by hemodialysis when administered as amphotericin B desoxycholate.
 
'''Pediatric and Elderly Patients:'''  The pharmacokinetics and pharmacodynamics of pediatric patients (≤16 years of age) and elderly patients (≥65 years of age) have not been studied.<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  |title = ABELCET (AMPHOTERICIN B, DIMYRISTOYLPHOSPHATIDYLCHOLINE, DL- AND DIMYRISTOYLPHOSPHATIDYLGLYCEROL, DL-) INJECTION [SIGMA-TAU PHARMACEUTICALS, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5587db37-f21a-4a39-a319-e1077032ced9 | publisher =  | date =  | accessdate =  }}</ref>


==References==
==References==

Latest revision as of 05:32, 10 January 2014

Amphotericin B lipid complex
ABELCET® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

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 blood after the administration of ABELCET® does not distinguish amphotericin B that is complexed with the phospholipids of ABELCET® from amphotericin B that is uncomplexed.

The pharmacokinetics of amphotericin B after the administration of ABELCET® are nonlinear. Volume of distribution and clearance from blood increase with increasing dose of ABELCET®, resulting in less than proportional increases in blood concentrations of amphotericin B over a dose range of 0.6-5 mg/kg/day. The pharmacokinetics of amphotericin B in whole blood after the administration of ABELCET® and amphotericin B desoxycholate are:

The large volume of distribution and high clearance from blood of amphotericin B after the admistration of ABELCET® probably reflect uptake by tissues. The long terminal elimination half-life probably reflects a slow redistribution from tissues. Although amphotericin B is excreted slowly, there is little accumulation in the blood after repeated dosing. AUC of amphotericin B increased approximately 34% from day 1 after the administration of ABELCET® 5 mg/kg/day for 7 days. The effect of gender or ethnicity on the pharmacokinetics of ABELCET® has not been studied.

Tissue concentrations of amphotericin B have been obtained at autopsy from one heart transplant patient who received three doses of ABELCET® at 5.3 mg/kg/day:

This pattern of distribution is consistent with that observed in preclinical studies in dogs in which greatest concentrations of amphotericin B after ABELCET® administration were observed in the liver, spleen, and lung; however, the relationship of tissue concentrations of amphotericin B to its biological activity when administered as ABELCET® is unknown.

Special Populations

Hepatic Impairment: The effect of hepatic impairment on the disposition of ABELCET® is not known.

Renal Impairment: The effect of renal impairment on the disposition of ABELCET® is not known. The effect of dialysis on the elimination of ABELCET® has not been studied; however, amphotericin B is not removed by hemodialysis when administered as amphotericin B desoxycholate.

Pediatric and Elderly Patients: The pharmacokinetics and pharmacodynamics of pediatric patients (≤16 years of age) and elderly patients (≥65 years of age) have not been studied.[1]

References

  1. "ABELCET (AMPHOTERICIN B, DIMYRISTOYLPHOSPHATIDYLCHOLINE, DL- AND DIMYRISTOYLPHOSPHATIDYLGLYCEROL, DL-) INJECTION [SIGMA-TAU PHARMACEUTICALS, INC.]".

Adapted from the FDA Package Insert.