Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease.

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.