?-Methyl-digoxin
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Digitoxin
Color discrimination ability of 53 patients with congestive heart failure and 32 healthy volunteers treated with digoxin, digitoxin, or pengitoxin was determined with the Farnworth's Munsell 100 hue test. The patients had been treated with digitalis glycosides for several months prior to color vision testing. The volunteers received glycosides until a steady-state plasma concentration was reached. Glycoside plasma levels were measured by radioimmunoassay on the 3 days prior to color vision testing. The total error scores, indices of color discrimination, increased with the glycoside plasma levels. Subjects treated with digitoxin or pengitoxin exhibited no marked elevation in total error score at therapeutic concentrations, whereas 17 of 28 subjects with therapeutic digoxin plasma concentrations (less than 2.0 ng/ml) showed disturbed color discrimination. At toxic plasma levels all 5 digoxin-treated subjects, 7 of 13 digitoxin-treated subjects, and 3 of 8 pengitoxin-treated subjects showed impairment of color discrimination. The greater tendency of digoxin to impair color vision in comparison with digitoxin and pengitoxin may be related to a higher uptake or different distribution in the retina.
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Digitoxin
Digitoxigenin
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The authors investigated the cross-reactivity of the major known digoxin metabolites--digoxigenin, digoxigenin monodigitoxoside, digoxigenin bisdigitoxoside, and dihydrodigoxin--and of digitoxin in three 125I-radioimmunoassays and one enzyme immunoassay for digoxin. Digitoxin and dihydrodigoxin exhibit low cross-reactivity and nonparallel dilution responses for these assays. The cross-reactivities of the other three substances are significant for all assays studied with digoxigenin and monodigitoxoside having nonparallel and enhanced tracer displacement compared with digoxin itself. The authors demonstrate that because of nonparallel tracer displacement estimates of cross-reactivity calculated by the 50% displacement method fail to adequately predict the error induced in digoxin assays by digitoxin. They conclude that digoxin metabolites in serum are measured to various extents as the parent digoxin compound by all of the immunoassays they studied. In view of the varying biologic activity of digoxin metabolites and the large patient to patient variations in digoxin metabolism, the cross-reactivities the authors observe may help to explain the discrepancies in correlation of clinical response to measured serum digoxin values reported in other studies.
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Digitoxin
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Digitoxin
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The most common methods for measuring digoxin concentrations in serum are immunoassays. The prerequisite for exact determination of the digoxin value is an antibody that specifically binds digoxin. Because digitoxin differs from digoxin only in the C-12 hydroxy group, it is difficult to obtain anti-digoxin antibodies that do not cross-react with this compound. During the development of a fluorescence polarization immunoassay (FPIA) for digoxin, we investigated digoxin tracers with different structures. We found that in FPIA the digitoxin cross-reactivity of an antibody could be reduced by varying the structure of the tracer molecule.
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Abstract Digitoxin interference with radioimmunoassay of digoxin may present a problem in determining digoxin concentrations in the serum of patients treated with digitoxin less than four weeks before digoxin was administered. Digoxin and digitoxin values were determined in the sera of 54 patients who were receiving only digitoxin. Additionally, digoxin was added to aliquots of sera from a patient receiving digitoxin, and digoxin concentrations were determined by radioimmunoassay. Digitoxin interfered with radioimmunoassay of digoxin in that 9% of the digitoxin present was counted as digoxin. The resulting spuriously high value for measured digoxin in patients receiving digoxin, but treated with digitoxin previously, can be corrected by applying the following equation (units: µg/liter): Digoxin (corrected) = digoxin (measured) — [0.09 x digitoxin (measured)]. This correction, which may differ somewhat with batch of antiserum, is applicable for digitoxin concentrations up to about 50 ng/ml. Digoxin does not interfere with the digitoxin assay.
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