Amphotericin B clinical pharmacology: Difference between revisions
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==Clinical Pharmacology== | |||
===Pharmacokinetics=== | |||
<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> | 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: | |||
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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== | ||
Revision as of 16:24, 4 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 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
Adapted from the FDA Package Insert.