深在性真菌症患者におけるLiposomal Amphotericin B（L-AMB）の薬物動態および安全性の検討

深在性真菌症罹患患者32名（23～73歳）を対象にLiposomal amphotericin B（L-AMB）を1.0 mg/kg/日，2.5 mg/kg/日または5.0 mg/kg/日の用量で原則7日間連日点滴静注し，薬物動態と安全性を検討した。L-AMB投与1日目の薬物動態ではCmax（平均値±標準偏差）は1.0 mg/kg/日，2.5 mg/kg/日，5.0 mg/kg/日の各用量でそれぞれ5.96±3.02 μg/mL，16.19±7.41 μg/mL，45.71±20.14 μg/mL，また，AUC0-24（平均値±標準偏差）では55.5±39.0 μg・hr/mL，138.5±56.5 μg・hr/mL，390.3±223.2 μg・hr/mLと用量が増すにつれ増加したが，投与量に対し非線形的な相関を示した。副作用は，用量が増すにつれ種類，頻度が増加する傾向にあった。1.0 mg/kg/日投与群で14例中10例（71.4％），2.5 mg/kg/日投与群で9例中8例（88.9％），5.0 mg/kg/日投与群で9例中9例（100％）であった。しかし，本剤の投与を制限する重篤な副作用は認められず，1.0 mg/kg/日～5.0 mg/kg/日を連日投与した場合の安全性と忍容性が確認された。
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 AUC0-24 (mean ± SD) was 55.5 ± 39.0, 138.5 ± 56.5, and 390.3 ± 223.2 μg・hr/mL, respectively. The Cmax and AUC0-24 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.