Trade & Generic Names & General Features
Amphotericin B lipid complex (ABLC) is a lipid formulation of amphotericin B. As with the other lipid formulations, the major goal of developing ABLC has been to attain a compound with lower toxicity and with at least similar efficacy compared to the parent compound, amphotericin B deoxycholate.
ABLC is composed of amphotericin B complexed with dymyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol [1044, 2454]. The configuration of this complex is ribbon-like. ABLC is now being manufactured by Enzon Pharmaceuticals (Fairfield, New Jersey, USA) and its trade name is Abelcet.
Amphotericin B concentrations achieved in blood after administration of ABLC are lower compared to that with amphotericin B deoxycholate. On the other hand, ABLC produces higher concentrations in liver, spleen, and lungs. The renal concentration, on the other hand, is similar for the two formulations. Importantly, when ABLC is administered at higher doses, its concentration in kidneys increases only slightly and that in plasma remains the same [1113, 1687].
The (E):CLEAR II™ (Collaborative Exchange of Antifungal Research) registry is an observational epidemiologic analysis of normal practice patterns in patients with invasive fungal infections. CLEAR II™ is an expansion of the original CLEAR® registry, which collected information on over 3500 patients with invasive fungal infections (IFIs) from 1996 to 2000.
Mechanism(s) of Action
The mechanism of action and intrinsic antifungal activity of ABLC is the same as the parent compound, amphotericin B .
The significance of susceptibility testing for ABLC, as for that of any of the lipid formulations of amphotericin B, is not known. This is mainly due to the fact that the enhanced activity of lipid formulations of amphotericin B follows from the lesser toxicity of the lipid preparation. This permits administration of increased doses of amphotericin B and, presumably, increased delivery of active drug to sites of infection.
Nevertheless, comparative results have been reported . For Aspergillus spp., ranking of the in vitro activity of amphotericin B and its lipid formulations has been reported as amphotericin B deoxycholate = ABCD > L-AMB > ~ABLC . However, further work is needed to support the relevance of this data. In the interim, we believe that testing should simply be done with amphotericin B, the parent compound.
For susceptibility patterns of amphotericin B, see amphotericin B. For ABLC MICs obtained for various types of fungi, see susceptibility patterns and the N/A(L):susceptibility database.
ABLC is in general administered at a dose of 5 mg/kg . However, doses as high as 7 mg/kg has been safely used .
The actual mechanism by which ABLC reduces the toxicity of the conventional preparation has been a topic of interest. The ribbon-like configuration of ABLC is a tightly packed complex of amphotericin B with the lipid. This complex presumably provides decreased amount of free drug and may thus be responsible for the reduced toxicity of ABLC .
It is also noteworthy that, in contrast to conventional amphotericin B, pharmacokinetics and renal toxicity of ABLC remain independent of increases in total and LDL cholesterol levels .
Similar to the other lipid formulations, nephrotoxicity due to ABLC is less frequent compared to amphotericin B deoxycholate . Fever and severe respiratory insufficiency may be observed [810, 1356].
ABLC is administered intravenously.
ABLC is licensed to be used in treatment of invasive fungal infections when amphotericin B therapy fails or is unacceptably toxic. It is not a first-line drug for any of the fungal infections. Its use as an empirical therapeutic agent in febrile neutropenia and its potency compared to the other lipid formulations are under continuing investigation.
Please also see our discussion on cost analysis and pharmacoeconomic analysis of antifungal therapy.