Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections.
A pilot study with amphotericin B incorporated in sonicated liposomes (ampholiposomes) made of egg phosphatidylcholine, cholesterol and stearylamine in a molar ratio 4:3:1 was performed in cancer patients with fungal infections. Fifteen patients received a total of 117 intravenous infusions of ampholiposomes. The total dose of amphotericin B administered per patient ranged from 20 to 1004 mg (mean 472 mg). The number of infusions per patient varied from 1 to 20 (mean 8) and the duration of treatment from 1 to 29 days (mean 10 days). Infusion of doses up to 1.8 mg/kg was well tolerated. None of the common side-effects of Fungizone, the colloidal suspension of amphotericin B, occurred; it was noteworthy that patients had no renal function impairment. Serum amphotericin B concentrations given as ampholiposomes were much higher than those obtained with Fungizone. With a daily treatment schedule, peak and trough serum amphotericin B concentrations, as measured by HPLC, were 10 to 20 micrograms/ml and 5 to 10 micrograms/ml respectively; while they did not exceed 2 micrograms/ml and 1 microgram/ml with Fungizone. Amphotericin B given as ampholiposomes had a prolonged serum beta half-life (25.3 +/- 16.0 h). Higher serum antifungal activity was observed with ampholiposomes as compared to Fungizone. We concluded that ampholiposomes have a better therapeutic index than Fungizone.
Sculier
J P
JP
Service de Médecine, Institut J. Bordet, l'Université Libre de Bruxelles, Belgium.
Coune
A
A
Meunier
F
F
Brassinne
C
C
Laduron
C
C
Hollaert
C
C
Collette
N
N
Heymans
C
C
Klastersky
J
J
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000097:blood / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D008172:Lung Diseases, Fungal / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications*; D013010:Sonication; D013997:Time Factors
D008081:Liposomes; D000666:Amphotericin B