Absorption Distribution Metabolism and Excretion

Amphotericin B is primarily an intravenous drug; absorption from the intestinal tract is minimal. After infusion the drug is rapidly taken up by the liver and other organs and is then slowly released back into the circulation, where 90% of the drug is bound to protein. Its initial half-life is about 24 hours; the second elimination phase has a half-life of 15 days. The initial phase comprises elimination from both a central intravascular and a rapidly equilibrating extravascular compartment; the second, longer phase represents elimination from storage sites in a slowly equilibrating extravascular compartment.

Drug concentrations in pleural fluid, peritoneal fluid, synovial fluid, aqueous humor, and vitreous humor approach two-thirds of the serum concentration when local inflammation is present. Meningeal and am-niotic fluid penetration, with or without local inflammation, is uniformly poor. Measurement of serum, urine, or cerebrospinal fluid drug levels has not been used clinically.

The major route of elimination of amphotericin B is by metabolism, with little intact drug detected in urine or bile. About 5% of amphotericin B is excreted in the urine as active drug, with drug still detectable in the urine 7 or more weeks after the last dose. Serum levels are not elevated in renal or hepatic failure, and the drug is not removed by hemodialysis.

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