Liposomal and Lipid Formulations of Amphotericin B
- 77 Downloads
Amphotericin B remains a very important drug for the treatment of fungal infections despite its toxicity. Encapsulation of amphotericin B into liposomes appears to reduce the toxic effects and to improve the clinical efficacy, allowing higher dosages to be given. The exact mechanism behind the reduced toxicity is not yet known.
Amphotericin B is widely distributed after intravenous administration as the deoxycholate solubilisate. The highest concentrations are found in the liver, spleen and kidney. Protein binding and binding to the tissues is very high. The fate of the drug in the body is not known in detail. Renal and biliary excretion are both low and no metabolites have been identified. The drug is still detectable in the liver, spleen and kidney for as long as 1 year after stopping therapy.
The pharmacokinetics of the different liposomal amphotericin B or lipid complexes of amphotericin B, which were recently developed, are quite diverse. A number of these preparations, such as amphotericin B lipid complex (ABLC), ‘AmBisome’ and amphotericin B colloidal dispersion (ABCD) are in clinical development. Their pharmacokinetics depend to a large extent on the composition and particle size of the liposomes or lipid complexes. Relatively large structures such as ABLC are rapidly taken up by the mononuclear phagocyte system, whereas smaller liposomes remain in the circulation for prolonged periods. In all studies only the total amphotericin B (both free and liposome- or lipid-associated) concentrations were determined.
There is a need for studies correlating clinical efficacy and tolerability of liposomal amphotericin B with the pharmacokinetic properties of these formulations.
KeywordsClinical Pharmacokinetic Acquire Immune Deficiency Syndrome Liposomal Amphotericin Lipid Complex Mononuclear Phagocyte System
Unable to display preview. Download preview PDF.
- Barriere SL. Pharmacology and pharmacokinetics of traditional systemic antifungal agents. Pharmacotherapy 10 (Suppl.): 134–140, 1990Google Scholar
- De Wit S, Rossi C, Duchateau J, Braitman A, Gupta R, et al. Safety, tolerance and immunomodulatory effect of amphotericin B lipid complex in HIV infected subjects. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29–October 2, 1991. Abstract no. 288, p. 147, 1991Google Scholar
- Ellis ME, Al-Hokail AA, Clark HM. A study of rapid vs slow infusion of amphotericin B on toxicity, tolerance and efficacy. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29–October 2, 1991. Abstract no. 744, p. 223, 1991Google Scholar
- Graybill JR, Sharkey PK, Vincent D, Johnson E, Havard PF, et al. Amphotericin B lipid complex in treatment of cryptococcal meningitis in patients with AIDS. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29–October 2, 1991. Abstract no. 289, p. 147, 1991Google Scholar
- Gregoriadis G (Ed.) Liposome technology, Vols 1–3, CRC Press, Boca Raton, 1984Google Scholar
- Gregoriadis G (Ed.) Liposomes as drug carriers: recent trends and progress, J Wiley and Sons, Chichester, 1988Google Scholar
- Guo LG, Fielding RM, Gantz DL, Steiner J, Small DM. Structure of amphotericin B colloidal dispersion: a novel amphotericin B dosage form. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29–October 2, 1991. Abstract no. 221, p. 135, 1991Google Scholar
- Janoff AS. Liposomes and lipid structures as carriers of amphotericin B. European Journal of Clinical Microbiology and Infectious Diseases 9: 146–151, 1990Google Scholar
- Joly V, Bolard J, Saint-Julien L, Carbon C, Yeni P. Influence of phospholipid/amphotericin B ratio and phospholipid type on in vitro renal cell toxicities and fungicidal activities of lipid-associated amphotericin B formulation. Antimicrobial Agents and Chemotherapy 36: 262–266, 1992PubMedCrossRefGoogle Scholar
- Knight CG (Ed.) Liposomes: from physical structure to therapeutic applications, Elsevier, Amsterdam, 1981Google Scholar
- Lasic DD, Martin FJ, Gabizon A, Huang SK, Papahadjopoulos D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochimica Biophysica Acta, in press, 1992Google Scholar
- Llanos-Cuentas A, Chang J, Cieza I, Echevarria J, Garcia P, et al. Safety and tolerance of amphotericin B lipid complex vs Fungizone in patients with mucocutaneous leishmaniasis. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, October 21–24, 1990. Abstract no. 568, p. 181, 1990Google Scholar
- Naessander UK, Storm G, Peeters PA, Crommelin DJ. Liposomes. In Chasin & Langer (Eds) Biodegradable polymers as drug delivery systems, Chapter 8, pp. 261–338, Marcel Dekker Inc., New York, 1990Google Scholar
- New RPC. Liposomes: a practical approach. IRL Press, Oxford, 1990Google Scholar
- Sharkey PK, Lipke R, Renteria A, Galgiani J, Catanzaro A, et al. Amphotericin B lipid complex in treatment of coccidioidomycosis. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, September 29–October 2, 1991. Abstract no. 742, p. 222, 1991Google Scholar
- Storm G, Oussoren C, Peeters PAM. Safety of liposome administration. In Vigo-Pelfrey C (Ed.) Membrane lipid oxidation, Vol. III, pp. 239–263, CRC Press, Boca Raton, 1991Google Scholar
- Tollemar J, Ringden O, Tyden G. Liposomal amphotericin B (AmbiSome) treatment in solid organ and bone marrow transplant recipients: efficacy and safety evaluation. Clinical Transplantation 4: 167–176, 1990Google Scholar
- Zonneveld G, Crommelin DJA. Liposomes: parenteral administration to man. In Gregoriadis G (Ed.) Liposomes as drug carriers: recent trends and progress, J Wiley and Sons, Chichester, 1988Google Scholar