 |
|
|
|
|
|
 Introduction
Human
Veterinary
Environmental
Industrial
Agricultural
MSG
Introduction
Descriptions
Synonyms
Image Bank
Lecture Bank
Video Bank
Introduction
Susceptibility
MIC Database
Procedures
Histopathology
Introduction
Abbreviations
Links
CME
Conference
Highlights
Bibliography
Glossary
Good Books
Events Calendar
Introduction
Our Mission
Editorial Board
Editorial Staff
Supporters
Contributors
Legal Stuff
Privacy Policy
Kudos
Introduction
Descriptions
Synonyms
Image Bank
Lecture Bank
Video Bank
This page updated:
1/27/2007 9:23:00 AM
DoctorFungus - All Rights Reserved
© 2007 Copyright
& Privacy Policy
Site built and designed for doctorfungus by Webillustrated
|
 |
 |
|
|
You are here:
Drugs >
Medical
>
|
|
Amphotericin B lipid complex
(ABLC)
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 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.
The mechanism of action and intrinsic antifungal activity of ABLC is the same as the parent compound, amphotericin B [2232].
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 [1129]. 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 [1668]. 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 susceptibility database.
ABLC is in general administered at a dose of 5 mg/kg [72]. However, doses as high as 7 mg/kg has been safely used [1044].
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 [1113].
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 [2383].
Similar to the other lipid formulations, nephrotoxicity due to ABLC is less frequent compared to amphotericin B deoxycholate [72]. 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.
|
|
References
72. Anaissie, E. J., M. White, O. Uzun, C. Singer, G. P. Bodey, M. D, N. Azarnia, and G. Lopez-Berenstein. 1995. Amphotericin B lipid complex (ABLC) versus amphotericin B (AMB) for treatment of hematogenous and invasive candidiasis: A prospective, randomized, multicenter trial. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. LM21.
810. Garnacho-Montero, J., C. Ortiz-Leyba, J. L. G. Garmendia, and F. J. J. Jimenez. 1998. Life-threatening adverse event after amphoterin B lipid complex treatment in a patient treated previously with amphoterin B deoxycholate. Clin. Infect. Dis. 26:1016.
1044. Hiemenz, J. W., and T. J. Walsh. 1996. Lipid formulations of amphotericin B: Recent progress and future directions. Clin. Infect. Dis. 22:S133-S144.
1113. Janoff, A. S., W. R. Perkins, S. L. Saleton, and C. E. Swenson. 1993. Amphotericin B lipid complex (ABLC): a molecular rationale for the attenuation of amphotericin B-related toxicities. Journal of Liposome Research. 3:451-472.
1129. Johnson, E. M., J. O. Ojwang, A. Szekely, T. L. Wallace, and D. W. Warnock. 1998. Comparison of in vitro antifungal activities of free and liposome-encapsulated nystatin with those of four amphotericin B formulations. Antimicrob. Agents Chemother. 42:1412-1416.
1356. Lister, J. 1996. Amphotericin B lipid complex (Abelcet) in the treatment of invasive mycoses: the North American experience. Eur. J. Haematol. 56:18S-23S.
1668. Oakley, K. L., C. B. Moore, and D. W. Denning. 1999. Comparison of in vitro activity of liposomal nystatin against Aspergillus species with those of nystatin, amphotericin B (AB) deoxycholate, AB colloidal dispersion, liposomal AB, AB lipid complex, and itraconazole. Antimicrob. Agents Chemother. 43:1264-1266.
1687. Olsen, S. J., M. R. Swerdel, B. Blue, J. M. Clark, and D. P. Bonner. 1991. Tissue distribution of amphotericin B lipid complex in laboratory animals. Journal of Pharmacology. 43:831-835.
2232. Terrell, C. L., and C. E. Hughes. 1992. Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc. 67:69-91.
2383. Wasan, K. M., A. L. Kennedy, S. M. Cassidy, M. Ramaswamy, L. Holtorf, J. W. L. Chou, and P. H. Pritchard. 1998. Pharmacokinetics, distribution in serum lipoproteins and tissues, and renal toxicities of amphotericin B and amphotericin B lipid complex in a hypercholesterolemic rabbit model: Single- dose studies. Antimicrob. Agents Chemother. 42:3146-3152.
2454. Wong-Beringer, A., R. A. Jacobs, and B. J. Guglielmo. 1998. Lipid formulations of amphotericin B: Clinical efficacy and toxicities. Clin. Infect. Dis. 27:603-618.
|
|
|
 |
 |
Home |
Image Bank |
Lecture Bank |
Knowledgebase |
Site Map |
Contact Us |
The Fungi |
Mycoses |
Drugs |
Laboratory |
Education & Tools |
About Us
|
|
|
|