Bloom K E, Brewer G J, Magon A M, Wetterstroem N
Clin Pharmacol Ther. 1983 Apr;33(4):403-9. doi: 10.1038/clpt.1983.54.
The in vitro metabolizing method was modified and its ability to correctly identify eight known hemolytic and nine known nonhemolytic drugs of glucose-6-phosphate (G6PD)-deficient erythrocytes was evaluated. The technique is based on inducing in vitro drug metabolism by incubation of red cells and drug with a reduced NADP-generating system in the presence of phenobarbital-induced mouse liver microsomes. Thus, this system provides a model for in vivo metabolic function. The hemolytic potential of tested drugs is indicated by the extent of loss of reduced glutathione of G6PD-deficient erythrocytes during 60-min incubations. Complete agreement between the test and literature for nonhemolytic compounds was observed. The test also correctly identified six of the eight known hemolytic drugs and failed to identify two known hemolytic drugs (acetanilide and sulfacetamide). The test was also applied to 14 drugs about which there is uncertainty regarding hemolytic potential. Of the latter, DL-alpha-methyldopa; alpha-naphthol; beta-naphthol; 2,3, dimercaptopropanol; phenacetin; and menadione were found to react positively. We conclude that this in vitro assay system will be useful in predicting which new drugs will be hemolytic in G6PD-deficient patients.
对体外代谢方法进行了改进，并评估了其正确识别葡萄糖-6-磷酸脱氢酶（G6PD）缺乏红细胞的8种已知溶血药物和9种已知非溶血药物的能力。该技术基于在苯巴比妥诱导的小鼠肝微粒体存在下，通过将红细胞和药物与产生还原型辅酶Ⅱ（NADP）的系统一起孵育来诱导体外药物代谢。因此，该系统提供了一个体内代谢功能的模型。受试药物的溶血潜力通过G6PD缺乏红细胞在60分钟孵育期间还原型谷胱甘肽损失的程度来表示。观察到非溶血化合物的测试结果与文献完全一致。该测试还正确识别了8种已知溶血药物中的6种，未能识别2种已知溶血药物（乙酰苯胺和磺胺醋酰）。该测试还应用于14种溶血潜力不确定的药物。在后者中，发现DL-α-甲基多巴、α-萘酚、β-萘酚、2,3-二巯基丙醇、非那西丁和维生素K反应呈阳性。我们得出结论，这种体外检测系统将有助于预测哪些新药会在G6PD缺乏的患者中引起溶血。
