TISSUE DISTRIBUTION AND BIOACTIVITY OF AMPHOTERICIN-B ADMINISTERED IN LIPOSOMES TO CANCER-PATIENTS

Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes.Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate. © 1991 The British Society for Antimicrobial Chemotherapy.