Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Int J Antimicrob Agents. 2011 Nov;38(5):417-20. doi: 10.1016/j.ijantimicag.2011.07.004. Epub 2011 Aug 31.
Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has been shown to have a better safety profile than both the deoxycholate and lipid complex forms of amphotericin B; however, the frequency of major side effects is still unclear. Thus, the aim of the present study was to assess retrospectively the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia as well as the relationship between daily dose of L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre-treatment) and anaemia were observed in 7 and 10 of 21 adult patients, respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of L-AmB that are estimated to cause side effects of a low RBC count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day, respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of total bilirubin, γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7, 8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9 patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not caused in a dose-dependent manner. In conclusion, the present analyses showed that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult patients. It is important to pay attention to causing anaemia and thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and >3.0mg/kg/day, respectively.
脂质体两性霉素 B（L-AmB）的开发旨在降低副作用，与两性霉素 B 的去氧胆酸盐和脂质复合物形式相比，具有更好的安全性；然而，主要副作用的频率仍不清楚。因此，本研究旨在回顾性评估 L-AmB 诱导的贫血、血小板减少、肾毒性、肝毒性和低钾血症的频率，以及 L-AmB 日剂量与这些副作用之间的关系。21 例成年患者中，分别有 7 例和 10 例出现低红细胞（RBC）计数（治疗后/治疗前）和贫血。19 例成年患者中有 11 例出现血小板减少。估计导致低 RBC 计数、贫血和血小板减少的 L-AmB 剂量分别为 4.0、3.3 和 3.0mg/kg/天，导致这些副作用的概率为 50%。22 例患者中有 6 例出现肾毒性。6 例患者的总胆红素、γ-谷氨酰转肽酶、天冬氨酸转氨酶和丙氨酸转氨酶的变化被用作肝毒性的指标，分别为 22 例中的 6、7、8 和 8 例。9 例患者中有 4 例出现低钾血症；然而，肾毒性、肝毒性和低钾血症不是剂量依赖性的。总之，本分析表明 L-AmB 剂量依赖性地诱导成年患者贫血和血小板减少。当患者接受 L-AmB 治疗时，分别在剂量大于 3.3mg/kg/天和大于 3.0mg/kg/天时，应注意引起贫血和血小板减少。
