Serum pharmacology of amphotericin B applied in lipid emulsions
Serum pharmacology of amphotericin B applied in lipid emulsions
复制标题
两性霉素B在脂质乳剂中应用的血清药理学
DOI：
10.1128/aac.41.4.728
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发表时间：
1997
影响因子：
4.9
通讯作者：
Wolfgang Wilmanns
中科院分区：
文献类型：
--
作者：
Volker Heinemann;B. Kähny;Ulrich Jehn;Dieter Mühlbayer;Alexander Debus;Kirsten Wachholz;Daniel Bosse;HANS;Wolfgang Wilmanns
与在5%葡萄糖中应用的阿朴霉素B（AmB/G）相比，在脂肪乳剂中应用的阿朴霉素B（AmB/L）降低了体外膜毒性，并降低了阿朴霉素B相关的体内毒副作用。因此，对AmB/L和AmB/G的药理学参数进行了比较分析。对13例患者进行了分析，其中9例患者接受了AmB/G和AmB/L的后续治疗。在两个治疗组的患者中，两性霉素B显示出从血清中的双相消除，终末半衰期延长至约27小时。与用剂量范围为0.6至1.5 mg/kg体重的AmB/G治疗的相同患者的值相比，用AmB/L治疗的患者显示出显著较低的峰浓度（44.2%; P = 0.008）和相应较低的药物浓度-时间曲线下面积（AUC）值（64.3%; P = 0.015）。AmB/L清除率的增强可能是由于网状内皮系统对阿替霉素B-脂质聚集体的初始消除更快。血清中较低的峰浓度和AUC值以及组织中AmB/L的相应较快沉积可至少部分解释AmB/L的较低毒性。对1例接受AmB/L治疗的患者的数据进行的比较药代动力学分析表明，血液透析对阿替霉素B的分布无显著影响。
Application of amphotericin B in lipid emulsions (AmB/L) reduced membrane toxicity in vitro and decreased amphotericin B-associated toxic side effects in vivo when compared to that of amphotericin B applied in 5% glucose (AmB/G). Therefore, a comparative analysis of the pharmacological parameters of AmB/L and AmB/G was performed. Thirteen patients were analyzed, and nine of these patients received a subsequent treatment with AmB/G and AmB/L. In patients in both treatment groups amphotericin B showed a biphasic elimination from serum, with a prolonged terminal half-life of approximately 27 h. Patients treated with AmB/L showed significantly lower peak concentrations (44.2%; P = 0.008) and correspondingly lower area under the drug concentration-time curve (AUC) values (64.3%; P = 0.015) compared to the values for the same patients treated with AmB/G at a dose range of 0.6 to 1.5 mg/kg of body weight. The enhanced clearance of AmB/L may be due to a faster initial elimination of amphotericin B-lipid aggregates by the reticuloendothelial system. Lower peak concentrations and AUC values in serum and a correspondingly faster deposition of AmB/L in tissues may at least partly explain the lower toxicity of AmB/L. A comparative pharmacokinetic analysis with data for a single patient treated with AmB/L demonstrated that hemodialysis did not significantly affect the disposition of amphotericin B.