Vogelsinger Helene, Weiler Stefan, Djanani Angela, Kountchev Jordan, Bellmann-Weiler Rosa, Wiedermann Christian J, Bellmann Romuald
Clinical Pharmacokinetics Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria.
J Antimicrob Chemother. 2006 Jun;57(6):1153-60. doi: 10.1093/jac/dkl141. Epub 2006 Apr 20.
Tissue concentrations of amphotericin B were determined in autopsy material of patients who had been treated with liposomal amphotericin B or amphotericin B colloidal dispersion (colloidal amphotericin B) for suspected or proven invasive fungal infection.
Amphotericin B tissue levels were measured in liver, spleen, lung, kidney, and myocardial and brain tissue of 20 patients who had been treated with lipid-formulated amphotericin B, before they died from multi-organ failure. Seven patients had been treated with liposomal amphotericin B (AmBisome) and thirteen with colloidal amphotericin B (Amphocil). Tissue samples were obtained during routine autopsy, homogenized and extracted with methanol. Amphotericin B concentrations were measured using HPLC after purification by solid phase extraction.
The highest amphotericin B levels were found in liver and spleen, followed by kidney, lung, myocardium and brain. In the lung higher amphotericin B concentrations were found after treatment with amphotericin B colloidal dispersion than after therapy with liposomal amphotericin B.
The choice of lipid formulation may influence amphotericin B penetration into the lung.
在因疑似或确诊侵袭性真菌感染而接受脂质体两性霉素B或两性霉素B胶体分散液(胶体两性霉素B)治疗的患者尸检材料中测定两性霉素B的组织浓度。
在20例因多器官功能衰竭死亡、曾接受脂质体两性霉素B治疗的患者的肝脏、脾脏、肺、肾脏、心肌和脑组织中测量两性霉素B的组织水平。7例患者接受脂质体两性霉素B(安必素)治疗,13例接受胶体两性霉素B(两性霉素B胶体)治疗。在常规尸检期间获取组织样本,匀浆并用甲醇提取。通过固相萃取纯化后,使用高效液相色谱法测量两性霉素B浓度。
两性霉素B水平在肝脏和脾脏中最高,但在肾脏、肺、心肌和脑组织中也有发现。在肺中,接受两性霉素B胶体分散液治疗后发现的两性霉素B浓度高于接受脂质体两性霉素B治疗后发现的浓度。
脂质制剂的选择可能会影响两性霉素B在肺中的渗透。