Stone J, Bentur Y, Zalstein E, Soldin S, Giesbrecht E, Koren G
Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
J Pediatr. 1990 Aug;117(2 Pt 1):321-5. doi: 10.1016/s0022-3476(05)80555-4.
The objective of this study was to assess the effect of endogenous digoxin-like substances on the interpretation of excessive concentrations of digoxin in children. After the development of a high-pressure liquid chromatography (HPLC) method for digoxin in our laboratories, we analyzed sera of children in whom the fluorescence polarization immunoassay identified potentially toxic concentrations of the glycoside (greater than 3 nmol/L; 2.3 ng/ml). Sixteen of them were receiving long-term digoxin therapy, and one had an accidental overdose. The immunoassay yielded significantly higher concentrations (4.1 +/- 1.2 nmol/L; 3.2 +/- 0.9 ng/ml) than the HPLC method (3.3 +/- 1.6 nmol/L; 2.6 +/- 1.2 ng/ml; p less than 0.01). In five cases (30%) these differences were clinically significant because administration of digoxin had been discontinued in the presence of true digoxin concentrations within the therapeutic range and the lack of clinical toxic effects. These data suggest that therapeutic drug monitoring using immunoassays of digoxin may be too inaccurate to detect potential toxic effects, and that much more weight should be focused on clinical monitoring. The HPLC method for assay of digoxin is extremely meticulous and will not become clinically available; therefore the development of better immunoassays should be encouraged.
本研究的目的是评估内源性地高辛样物质对儿童地高辛浓度过高解读的影响。在我们实验室开发出一种用于检测地高辛的高效液相色谱（HPLC）方法后，我们分析了那些荧光偏振免疫测定法鉴定出糖苷潜在中毒浓度（大于3 nmol/L；2.3 ng/ml）的儿童血清。其中16名儿童正在接受长期地高辛治疗，1名儿童意外过量服用。免疫测定法得出的浓度（4.1±1.2 nmol/L；3.2±0.9 ng/ml）显著高于HPLC法（3.3±1.6 nmol/L；2.6±1.2 ng/ml；p<0.01）。在5例（30%）病例中，这些差异具有临床意义，因为在实际地高辛浓度处于治疗范围内且无临床中毒效应的情况下已停用了地高辛。这些数据表明，使用地高辛免疫测定法进行治疗药物监测可能不准确，无法检测到潜在的中毒效应，而且应更加注重临床监测。用于检测地高辛的HPLC方法极其精细，尚无法临床应用；因此，应鼓励开发更好的免疫测定法。
