Pharmacokinetics of liposomal amphotericin B (AmBisome) in critically ill patients

Volker Heinemann, Daniel Bosse, Ulrich Jehn, Brigitte Kähny, Kirsten Wachholz, Alexander Debus, Priska Scholz, Hans Jochem Kolb, Wolfgang Wilmanns

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (C(max)) and areas under concentration- time curves (AUC) were 8- to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median C((max)s were 8.4-fold higher (14.4 versus 1.7 μg/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7- fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.

Original languageEnglish
Pages (from-to)1275-1280
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume41
Issue number6
DOIs
StatePublished - Jun 1997
Externally publishedYes

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