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JAC Advance Access originally published online on February 11, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 671-681
© 2003 The British Society for Antimicrobial Chemotherapy

Amphotericin B lipid formulations in critically ill patients on continuous veno-venous haemofiltration

Romuald Bellmann1,2,*, Petra Egger1,§, Walter Gritsch2, Rosa Bellmann-Weiler3, Michael Joannidis2, Nicole Kaneider1, Stefan Dunzendorfer1 and Christian J. Wiedermann1,2

1 Clinical Pharmacokinetics Unit, Medical Intensive Care Research Laboratory, Department of Internal Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck; 2 Intensive Care Unit, Department of Internal Medicine, University of Innsbruck; 3 Infectious Disease Unit, Division of General Internal Medicine, Department of Internal Medicine, University of Innsbruck, Austria

Received 17 August 2002; returned 4 November 2002; revised 9 December 2002; accepted 6 January 2003

Objectives: The pharmacokinetics of lipid-formulated amphotericin B (AMB), and of AMB that has dissociated from its lipid moiety and bound to lipoproteins in plasma, were separately determined in critically ill patients.

Patients and methods: Eleven patients required continuous veno-venous haemofiltration (CVVH). Five of them were treated with liposomal AMB (AmBisome) and seven with AMB colloidal dispersion (Amphocil). Six of the critically ill were not undergoing CVVH (three of them treated with liposomal AMB and three with AMB colloidal dispersion).

Results: Significant amounts of AMB are liberated from liposomes or colloidal dispersion during circulation in plasma, where pharmacokinetics mimic that of AMB deoxycholate. Elimination of the remaining lipid-formulated fraction is different and differentially affected by CVVH. Plasma levels of lipid-formulated AMB were significantly higher in patients treated with liposomal AMB than in those treated with AMB colloidal dispersion; clearance of liposomal AMB is enhanced by haemofiltration, whereas elimination of AMB colloidal dispersion is not significantly affected.

Conclusions: The pharmacokinetics of AMB that has been liberated from its lipid moiety is similar under treatment with either liposomal AMB or AMB colloidal dispersion. Since no significant influence of haemofiltration on the pharmacokinetics of liberated AMB has been found, a standard dose of lipid-formulated AMB can be recommended for patients on haemofiltration.

Keywords: pharmacokinetics, amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B colloidal dispersion

* Corresponding author. Tel: +43-512-504-4194; Fax: +43-512-504-4199; E-mail: romuald.bellmann{at}uibk.ac.at

§ Present address. Dipartimento di Ingegneria dei Materiali, Università di Trento, via Mesiano 77, I-38050 Trento, Italy.


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