Pharmacology of amphotericin B
- Richard H Drew, PharmD, MS, FCCP
Richard H Drew, PharmD, MS, FCCP
- Professor, Campbell University College of Pharmacy and Health Sciences
- Associate Professor and Clinical Pharmacist, Infectious Diseases
- Duke University Medical Center
Amphotericin B is a polyene antifungal agent with activity in vitro against a wide variety of fungal pathogens . Amphotericin B exerts its antifungal effect by disruption of fungal cell wall synthesis because of its ability to bind to sterols, primarily ergosterol, which leads to the formation of pores that allow leakage of cellular components. This affinity may also account for its toxic effects against select mammalian cells. Amphotericin B is generally considered cidal against susceptible fungi at clinically relevant concentrations.
Despite the introduction of newer antifungal agents for the treatment of systemic mycoses, amphotericin B remains the standard treatment for many severe, invasive fungal infections. However, because of toxicities associated with its intravenous use, along with the expanded availability of safer treatment options, it is frequently reserved for patients who have severe, life-threatening invasive fungal infections or who are unable to tolerate alternative antifungal agents.
The pharmacology of amphotericin B will be reviewed here. The nephrotoxicity and the clinical uses of amphotericin B are discussed in detail elsewhere. (See "Amphotericin B nephrotoxicity" and "Treatment of candidemia and invasive candidiasis in adults" and "Chronic disseminated candidiasis (hepatosplenic candidiasis)" and "Candida infections of the bladder and kidneys" and "Candida osteoarticular infections" and "Treatment of endogenous endophthalmitis due to Candida species" and "Treatment of exogenous endophthalmitis due to Candida species" and "Candida endocarditis and suppurative thrombophlebitis" and "Mucormycosis (zygomycosis)" and "Treatment and prevention of invasive aspergillosis" and "Treatment and prevention of Fusarium infection" and "Cryptococcus neoformans: Treatment of meningoencephalitis and disseminated infection in HIV seronegative patients" and "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Cryptococcus neoformans infection outside the central nervous system" and "Treatment of blastomycosis" and "Diagnosis and treatment of pulmonary histoplasmosis" and "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients" and "Diagnosis and treatment of histoplasmosis in HIV-infected patients" and "Management of pulmonary sequelae and complications of coccidioidomycosis" and "Manifestations and treatment of extrapulmonary coccidioidomycosis" and "Coccidioidomycosis in compromised hosts" and "Coccidioidal meningitis" and "Treatment of sporotrichosis".)
SPECTRUM OF ACTIVITY
Activity of amphotericin B has been demonstrated in vitro against a wide variety of clinical fungal isolates, including most Candida spp, Aspergillus spp, the Mucorales, all of the endemic mycoses, and most hyaline and brown-black molds. Activity has also been demonstrated against Leishmania spp .
Organisms that are usually resistant to amphotericin B include the organisms that cause chromoblastomycosis, Aspergillus terreus, Candida lusitaniae, Scedosporium spp, and some Fusarium spp [2-6].
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- SPECTRUM OF ACTIVITY
- AMPHOTERICIN B DEOXYCHOLATE
- - Absorption
- - Distribution
- - Metabolism/elimination
- Method of administration
- - Intravenous
- - Bladder irrigation
- - Intraperitoneal
- - Intrathecal
- - Intravitreal
- - Aerosolized/nebulized
- Adverse effects
- - Infusion-related reactions
- - Nephrotoxicity
- - Electrolyte abnormalities
- - Other reactions
- Patient monitoring
- LIPID-BASED AMPHOTERICIN B FORMULATIONS
- Safety and efficacy
- Amphotericin B plus fat emulsions
- DRUG INTERACTIONS