Serum pharmacology of amphotericin B applied in lipid emulsions.
Application of amphotericin B in lipid emulsions (AmB/L) reduced membrane toxicity in vitro and decreased amphotericin B-associated toxic side effects in vivo when compared to that of amphotericin B applied in 5% glucose (AmB/G). Therefore, a comparative analysis of the pharmacological parameters of AmB/L and AmB/G was performed. Thirteen patients were analyzed, and nine of these patients received a subsequent treatment with AmB/G and AmB/L. In patients in both treatment groups amphotericin B showed a biphasic elimination from serum, with a prolonged terminal half-life of approximately 27 h. Patients treated with AmB/L showed significantly lower peak concentrations (44.2%; P = 0.008) and correspondingly lower area under the drug concentration-time curve (AUC) values (64.3%; P = 0.015) compared to the values for the same patients treated with AmB/G at a dose range of 0.6 to 1.5 mg/kg of body weight. The enhanced clearance of AmB/L may be due to a faster initial elimination of amphotericin B-lipid aggregates by the reticuloendothelial system. Lower peak concentrations and AUC values in serum and a correspondingly faster deposition of AmB/L in tissues may at least partly explain the lower toxicity of AmB/L. A comparative pharmacokinetic analysis with data for a single patient treated with AmB/L demonstrated that hemodialysis did not significantly affect the disposition of amphotericin B.
Heinemann
V
V
Klinikum Grosshadern, III Medical Clininc, University of Munich, Germany.
Kähny
B
B
Jehn
U
U
Mühlbayer
D
D
Debus
A
A
Wachholz
K
K
Bosse
D
D
Kolb
H J
HJ
Wilmanns
W
W
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004655:Emulsions; D004910:Erythrocyte Membrane / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D000666:Amphotericin B