Vol.61 No.4 July 2013

Evaluation of pharmacokinetics and safety of liposomal amphotericin B (L-AMB) in patients with deep-seated fungal infection

Shigeru Kohno¹⁾, Hiroyuki Kobayashi²⁾, Toru Masaoka³⁾, Akio Urabe⁴⁾, Akihisa Kanamaru⁵⁾, Yoshihito Niki⁶⁾, Takeshi Mori⁷⁾, Kohei Hara⁸⁾, Hideo Ikemoto⁹⁾, Takashi Maniwa¹⁰⁾, Eiji Nakajo¹⁰⁾, Kota Suzuki¹⁰⁾ and Hideyo Yamaguchi¹¹⁾

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

The pharmacokinetics and safety of liposomal amphotericin B (L-AMB) were evaluated in 32 patients with deep-seated fungal infections (age, 23-73 years) after intravenous infusion at a dose of 1.0, 2.5, or 5.0 mg/kg/day for seven consecutive days. On Day 1 of treatment with L-AMB at doses of 1.0, 2.5, and 5.0 mg/kg/day, the Cmax (mean±standard deviation [SD]) was 5.96±3.02, 16.19±7.41, and 45.71±20.14 μg/mL, respectively, and the AUC_0-24(mean±SD) was 55.5±39.0, 138.5±56.5, and 390.3±223.2 μg·hr/mL, respectively. The Cmax and AUC_0-24 increased with increasing doses, but not in a linear manner. The type and incidence of adverse drug reactions tended to increase with increasing doses. Adverse drug reactions were reported in 10 (71.4%) of the 14 subjects in the 1.0-mg/kg/day group, 8 (88.9%) of the 9 subjects in the 2.5-mg/kg/day group, and all (100%) of the 9 subjects in the 5.0-mg/kg/day group. However, no serious, dose-limiting adverse drug reactions occurred, demonstrating the safety and tolerability of daily treatment with L-AMB at doses of 1.0 to 5.0 mg/kg/day.

Key word

deep-seated fungal infection, liposomal amphotericin B, pharmacokinetics

Received

October 22, 2012

Accepted

May 23, 2013

Jpn. J. Chemother. 61 (4): 369-379, 2013