Biomedical subjects

C Heymans

Publications and source records attributed to C Heymans.

18 recordsLinked to original sources

PubMed1990

In-vitro evaluation of the antifungal activity of amphotericin B entrapped into liposomes during storage for one year.

The stability of the antifungal activity of amphotericin B entrapped in small sonicated liposomes (ampholiposomes) was studied in vitro over a one-year period. Preparations of ampholiposomes stored at -20 degrees C or at 4 degrees C were compared monthly with freshly-prepared ampholiposomes and a commercial preparation of amphotericin B-deoxycholate (Fungizone; Squibb) by a killing curve method with Candida albicans. The bioactivity of the four preparations, each containing 1.5 or 2 mg/l of amphotericin B, was measured as the initial rate of killing and the 'relative bioactivity'. Relative bioactivity was calculated as the percentage reduction of the area under the growth curve compared with control growth. Storage of ampholiposomes for one year did not decrease their antifungal activity. Storage of ampholiposomes containing 1.5 mg/l amphotericin B for one year at -20 degrees C, but not at 4 degrees C, gave a significant increase in relative bioactivity and killing rate in comparison with freshly-prepared ampholiposomes. This was probably due to modifications in the spatial configuration of phospholipids and amphotericin B. The persisting antifungal activity of ampholiposomes stored for one year should allow the preparation of large batches to perform comparative clinical studies.

Amphotericin B↗

PubMed1989

Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B-deoxycholate.

We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection. Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts. The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillus fumigatus. Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 micrograms/g. A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs. Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates. Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys. The median concentration in bile was 7.3 micrograms/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose. Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC. In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive.

Adult↗

PubMed1988

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.

Adult↗

PubMed1986

In vitro evaluation of various antifungal agents alone and in combination by using an automatic turbidimetric system combined with viable count determinations.

A new method combining automatic turbidimetry and sequential viable count determinations was developed to evaluate the in vitro activity of various antifungal agents alone and in combination against three clinical isolates of Candida spp. (two Candida albicans and one C. tropicalis) at two inocula (10(-5) and 10(-6) CFU/ml). Specific parameters were derived from the time-kill curves: the maximal rate of killing, the lowest biomass, and the overnight biomass. Their intra-assay and between-assay reproducibilities were high, with respective standard deviations of 0.4 and 0.25 to 1.4 log CFU/ml. Amphotericin B alone showed a linear relationship between rate of killing or lowest biomass and the log of concentration from 0.03 to 4 mg/liter that was similar for the three strains tested. 5-Fluorocytosine (flucytosine) alone showed a dose-related reduction of overnight biomass for concentrations up to 8 mg/liter with no further increase at higher concentrations for one strain of C. albicans and a paradoxical decrease for one strain of C. tropicalis. Ketoconazole alone was found to be only fungistatic with no increased activity at concentrations up to 16 mg/liter. Amphotericin B plus flucytosine interacted synergistically in 46 to 60% of the combinations tested against C. tropicalis depending on the initial inoculum. Indifference was observed for the two strains of C. albicans. Amphotericin B or flucytosine plus ketoconazole was usually indifferent against the three tested strains.

Amphotericin B↗

PubMed1968