Vol.61 No.4 July 2013
Evaluation of efficacy and safety of liposomal amphotericin B (L-AMB) in deep-seated fungal infection
1)Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Japan
(Past: Second Department of Internal Medicine, Nagasaki University Hospital)
2)Professor Emeritus at Kyorin University
3)Consultant at Osaka Medical Center for Cancer and Cardiovascular Diseases
4)Consultant at NTT Medical Center Tokyo
(Past: Division of Hematology, NTT Medical Center Tokyo)
5)Institute of Life Science, Kinki University
(Past: Department of Hematology, Nephrology and Rheumatology, Department of Internal Medicine, Kinki University Hospital)
6)Department of Clinical Infectious Diseases, Showa University School of Medicine
(Past: Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School)
7)Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine
8)Professor Emeritus at Nagasaki University
9)Professor Emeritus at Juntendo University
10)Dainippon Sumitomo Pharma Co., Ltd.
11)Professor Emeritus at Teikyo University
Abstract
A multicenter, uncontrolled study of liposomal amphotericin B(L-AMB) was conducted in patients with deep-seated fungal infection. Patients with a suspected or confirmed diagnosis of fungal infection were included in the study, and the efficacy, safety, and pharmacokinetics of once-daily intravenous infusion of L-AMB were evaluated. After treatment was started at a dose of 2.5 mg/kg, the dose could be increased to 5.0 mg/kg or reduced to 1.0 mg/kg. Of 88 subjects treated, 86 subjects were included in the safety analysis population, and 66 subjects were included in the efficacy analysis population.
The efficacy rate (primary endpoint: overall efficacy) was 63.6% (42/66) in the entire population. The efficacy rate in patients grouped by fungal disease was 66.7% for candidiasis (8/12), 51.4% (18/35) for aspergillosis, 100% (1/1) for cryptococcosis, 0% (0/2) for mixed mycosis, and 93.8% (15/16) for suspected mycosis. The efficacy rate was 62.3% (33/53) in subjects unresponsive to other antifungal agents and 70.5% (31/44) in subjects with concomitant hematopoietic malignancy.
In 19 subjects from whom the causative fungus was isolated, the fungal elimination rate was 63.2% (12/19): 100% (7/7) in patients with candidiasis and 41.7% (5/12) in patients with aspergillosis. The MIC of L-AMB in clinical isolates of Candida spp. and Aspergillus spp. (in μg/mL) was 0.5-4 and ≤0.12-1, respectively.
A total of 664 adverse events possibly related to L-AMB (adverse drug reactions) were reported in 82 (95.3%) of 86 subjects. The most common adverse drug reactions with an incidence of ≥10% included nausea, pyrexia, increased serum creatinine, increased BUN, and decreased serum potassium. Most of these adverse drug reactions were mild or moderate in severity.
Serum trough concentrations were measured in 78 subjects and increased in 8 of these subjects. In plasma, 89.1% of amphotericin B was found in the liposomal form.
By demonstrating the efficacy, safety, and pharmacokinetics of L-AMB in patients with deep-seated fungal infection, these results indicate the clinical usefulness of L-AMB in the treatment of deep-seated fungal infection.
Key word
deep-seated fungal infection, liposomal amphotericin B
Received
October 22, 2012
Accepted
May 17, 2013
Jpn. J. Chemother. 61 (4): 347-368, 2013
