Liposomal and Lipid Formulations of Amphotericin B View Full Text


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Article Info

DATE

1992-10

AUTHORS

Robert Janknegt, Siem de Marie, Irma A. J. M. Bakker-Woudenberg, Daan J. A. Crommelin

ABSTRACT

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. More... »

PAGES

279-291

References to SciGraph publications

  • 1983-08. Elimination of amphotericin B in impaired renal function in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1988-05. Liposomes as drug delivery system in the treatment of infectious diseases potential applications and clinical experience in INFECTION
  • 1983-02. Clinical Pharmacokinetics of Systemic Antifungal Drugs in CLINICAL PHARMACOKINETICS
  • 1989. Liposomes and Lipid Structures as Carriers of Amphotericin B in PERSPECTIVES IN ANTIINFECTIVE THERAPY
  • 1991-09. Liposomal Drug Delivery in CLINICAL PHARMACOKINETICS
  • 1989-10. Successful treatment with liposomal amphotericin B in two patients with persisting fungemia in EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.2165/00003088-199223040-00004

    DOI

    http://dx.doi.org/10.2165/00003088-199223040-00004

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041292032

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/1395361


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