[Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy].
Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)
Chavanet
P
P
Service des Maladies Infectieuses et Tropicales, Hôpital du Bocage, Dijon.
Charlier
N
N
Brenet
A
A
Goux
A
A
Muggéo
E
E
Caillot
D
D
Casasnovas
O
O
Kistermann
J P
JP
Waldner
A
A
Portier
H
H
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology* / Q000506:poisoning / Q000627:therapeutic use; D000818:Animals; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D004338:Drug Combinations; D005950:Glucose Solution, Hypertonic; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008055:Lipids; D011817:Rabbits
D004338:Drug Combinations; D005950:Glucose Solution, Hypertonic; D008055:Lipids; D000666:Amphotericin B
Emulsion de l'amphotéricine B dans l'Intralipide 20%: efficacité in vitro et in vivo.