Antifungalactivity

Amphotericin B has useful clinical activity against a broad range of pathogenic fungi and against the protozoa, Leishmania braziliensis and Naegleria fowleri, but has no antibacterial activity. The antifungal activity of amphotericin B depends principally on binding the sterol ergosterol in the membrane of sensitive fungi. By virtue of interaction with sterols, amphotericin forms pores that increase membrane permeability and allow leakage of small molecules (Figure 48—1).

ABSORPTION, DISTRIBUTION, AND EXCRETION Gastrointestinal (GI) absorption of amphotericin B is negligible and intravenous delivery is used. Amphotericin B in plasma is >90% bound to proteins. Drug elimination apparently is unchanged in anephric patients and those on hemodialysis. Hepatic or biliary disease has no known effect on drug metabolism in humans. The terminal phase of elimination has a t1/2 of ~15 days. Concentrations of amphotericin B in fluids from inflamed pleura, peritoneum, synovium, and aqueous humor are approximately two-thirds of plasma trough concentrations. Little amphotericin B penetrates into cerebrospinal fluid (CSF), vitreous humor, or amniotic fluid.

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