Dorn A, Graf N, Pees H W
Universitätsklinik für Kinder- und Jugendmedizin, Homburg/Saar, Bundesrepublik Deutschland.
Padiatr Padol. 1993;28(6):157-63.
The intracellular drug uptake of anthracycline antibiotics, including the anthrachinone analogue mitoxantrone, was investigated. Measurement of drug uptake for each of the white cell subpopulations is possible by Flow cytometry (FCM). Cell separation was carried out by two different methods, using Lysing solution and Ficoll. Ficoll was found to be the best for further investigations in cell kinetics. Stock solutions of each drug, ranging from 0.5-3 micrograms/ml, were incubated with cell suspensions of healthy donors. In the case of doxorubicin, daunorubicin and epirubicin a linear correlation between drug concentration in the incubation medium and intracellular drug level was found. In further studies drug concentration was constant (1 microgram/ml or 3 micrograms/ml) and the intracellular drug uptake was measured at various incubation times. Examinations were carried out with the two different cell separation methods, mentioned above. In healthy donors the reproducibility of FCM measurement was examined. In conclusions of the results observed in experiments, FCM seems to be a suitable, reproducible technique for determination of cellular anthracycline concentrations with the exclusion of aclacinomycin A and mitoxantrone because of their physical properties.
研究了包括蒽醌类似物米托蒽醌在内的蒽环类抗生素的细胞内药物摄取情况。通过流式细胞术(FCM)可以对每个白细胞亚群的药物摄取进行测量。使用裂解液和菲可(Ficoll)通过两种不同方法进行细胞分离。发现菲可对于细胞动力学的进一步研究是最佳的。将浓度范围为0.5 - 3微克/毫升的每种药物储备液与健康供体的细胞悬液一起孵育。对于阿霉素、柔红霉素和表柔比星,发现在孵育培养基中的药物浓度与细胞内药物水平之间存在线性相关性。在进一步的研究中,药物浓度保持恒定(1微克/毫升或3微克/毫升),并在不同的孵育时间测量细胞内药物摄取。使用上述两种不同的细胞分离方法进行检测。在健康供体中检测了FCM测量的可重复性。根据实验中观察到的结果得出结论,由于阿克拉霉素A和米托蒽醌的物理性质,FCM似乎是一种适用于测定细胞内蒽环类药物浓度的可重复技术,但不包括这两种药物。