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

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

105 Zitate (Scopus)


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.

Seiten (von - bis)1275-1280
FachzeitschriftAntimicrobial Agents and Chemotherapy
PublikationsstatusVeröffentlicht - Juni 1997
Extern publiziertJa


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