A simple, rapid, and reliable determination of plasma digitoxin levels is now available for clinical use. It can be determined in any clinical laboratory capable of determining a serum phosphorus if ATPase enzyme is available. Maintenance plasma levels range between 10 and 40 mµg/ml with a mean value of 25 mµg/ml. There is overlapping of maintenance and toxic serum levels in the higher ranges. Values over 45 mµg/ml warrant careful evaluation for digitalis intoxication.
Maintenance plasma levels can be achieved with or without the usual digitalizing dosage if time is not a factor. The daily regression rate is variable in cases of digitalis intoxication following drug withdrawal.
ECG changes (the degree of ST-segment depression, PR-interval prolongation, and multifocal premature contractions) were not good criteria for digitalis intoxication, although PR intervals above 0.24 sec consistently correlated with high plasma digitoxin levels. Variable second and third degree A-V block associated with mental confusion was a frequent presenting feature of digitalis toxicity.
Digoxin-containing sera from 86 patients were analyzed for this drug by bioassay and radioimmunoassay. Each serum was analyzed in duplicate by six procedures: inhibition of Na+-K+-dependent ATPase and five "kit" radioimmunoassays from four different commercial sources. Mean values for two of the radioimmunoassays differed significantly from those for the bioassay. One radioimmunoassay mean value was significantly different from the other five mean values. We conclude that normal values for digoxin radioimmunoassay should be determined for each kit, and should not be adopted from published data.
Evaluation of commercial kits (3H and 125I digoxin) for the radioimmunoassay of digoxin showed that different normal plasma samples yielded significantly different standard assay curves. Such differences accounted for errors of from 0.6 to 1 ng under certain conditions. The usual internal assay controls do not correct for these conditions. Because such changes may represent the differences between toxic and nontoxic digoxin concentrations, further study of the commercial test procedures appears to be indicated.
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