Miller J J, Straub R W, Valdes R
Department of Pathology, University of Louisville School of Medicine, KY 40292.
Clin Chem. 1994 Oct;40(10):1898-903.
Our objective was to identify commercially available digoxin immunoassays whose cross-reactivity with digoxin metabolites paralleled the pharmacological activity of the metabolites. We measured the immunoreactivity of digoxigenin bis- and monodigitoxosides, digoxigenin, and dihydrodigoxin in four immunoassays and compared the immunoactivities with pharmacological activities from studies involving whole-animal and receptor (Na,K-ATPase)-based assays. Correlation coefficients for comparisons of immunoassay reactivity and human heart receptor reactivities were: ACS, 0.96; TDx, 0.60; Stratus, 0.57; and Magic, 0.42. Comparison with other biological assays showed a similar trend. The major difference in metabolite cross-reactivities among the immunoassays was that of digoxigenin (ACS, 0.7%; TDx, 103%; Stratus, 108%; Magic, 153%), which has approximately 10% bioactivity relative to digoxin. Measured recovery of mixtures of digoxin and metabolites confirmed these findings. We conclude that the monoclonal antibody in the ACS digoxin assay closely mimics Na,K-ATPase in detecting digoxin and its metabolites. This finding provides a basis for developing therapeutic drug monitoring immunoassays capable of approximating the true pharmacological activity of a mixture of drug metabolites.
我们的目标是鉴定市售的地高辛免疫测定法，其与地高辛代谢物的交叉反应性与代谢物的药理活性平行。我们在四种免疫测定法中测量了洋地黄毒苷双洋地黄毒糖苷和单洋地黄毒糖苷、洋地黄毒苷和二氢地高辛的免疫反应性，并将免疫活性与涉及全动物和基于受体（钠钾ATP酶）的测定研究中的药理活性进行了比较。免疫测定反应性与人心肌受体反应性比较的相关系数为：ACS为0.96；TDx为0.60；Stratus为0.57；Magic为0.42。与其他生物学测定的比较显示出类似趋势。免疫测定法中代谢物交叉反应性的主要差异在于洋地黄毒苷（ACS为0.7%；TDx为103%；Stratus为108%；Magic为153%），其相对于地高辛具有约10%的生物活性。地高辛及其代谢物混合物的实测回收率证实了这些发现。我们得出结论，ACS地高辛测定法中的单克隆抗体在检测地高辛及其代谢物时与钠钾ATP酶密切相似。这一发现为开发能够近似药物代谢物混合物真实药理活性的治疗药物监测免疫测定法提供了基础。
