Pharmacokinetics of liposomal amphotericin B (Ambisome) in critically ill patients.
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 (Cmax) 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 Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/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.
Heinemann
V
V
Klinikum Grosshadern, III Medical Clinic, University of Munich, Germany.
Bosse
D
D
Jehn
U
U
Kähny
B
B
Wachholz
K
K
Debus
A
A
Scholz
P
P
Kolb
H J
HJ
Wilmanns
W
W
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000097:blood / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D000981:Antiprotozoal Agents / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D003840:Deoxycholic Acid / Q000097:blood / Q000493:pharmacokinetics; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004338:Drug Combinations; D004347:Drug Interactions; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005260:Female; D006440:Hemofiltration; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged
D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D004337:Drug Carriers; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D008081:Liposomes; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination