Overview of amphotericin B colloidal dispersion (amphocil)

Area of Science:

• Mycology
• Pharmacology
• Infectious Diseases

Background:

• Amphotericin B is a critical antifungal agent, but its deoxycholate formulation is associated with significant toxicity.
• Amphotericin B colloidal dispersion (ABCD) is a novel formulation designed to improve the safety and stability profile of amphotericin B.

Purpose of the Study:

• To evaluate the preparation, stability, pharmacokinetics, in vitro activity, preclinical toxicology, and clinical efficacy and safety of Amphotericin B colloidal dispersion (ABCD).

Main Methods:

• Characterization of ABCD preparation and stability.
• Pharmacokinetic studies comparing ABCD to deoxycholate amphotericin B.
• In vitro susceptibility testing against various fungal isolates.
• Preclinical toxicology assessments in animal models.
• Phase I/II clinical trials in patients with invasive fungal infections.

Main Results:

• ABCD exhibits favorable preparation and stability, allowing higher intravenous doses.
• Pharmacokinetics show lower peak serum concentrations, similar AUC, and longer half-life compared to deoxycholate amphotericin B.
• Preclinical studies indicate a significantly improved safety factor and therapeutic ratio for ABCD, particularly in cryptococcosis models.
• Human studies demonstrated efficacy in coccidioidomycosis, candidiasis, and aspergillosis, with acceptable renal toxicity but common infusion-related side effects and anemia.

Conclusions:

• Amphotericin B colloidal dispersion (ABCD) presents a viable alternative for intravenous amphotericin B delivery with a potentially improved safety profile.
• Further comparative studies against deoxycholate amphotericin B are essential to establish the definitive clinical utility of ABCD.