Amphotericin B clinical pharmacology

Amphotericin B
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.

References

Adapted from the FDA Package Insert.