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SUMMARYSerum digoxin levels (SDL) were compared with tolerance for the rapidly acting cardiac aglycone, acetyl strophanthidin (AS). AS titration tests were performed on 133 patients with diverse cardiac disorders. All were receiving maintenance digoxin. Both exquisite AS sensitivity and tolerance for a 1.0 mg AS were associated with a wide range of SDL values. Concordance and discordance between the two methods in assessing degree of digitalization were evaluated by considering SDL of 1.4 ng/ml to be the mean value for patients without glycoside-induced cardiac arrhythmia. An SDL of <1.5 ng/ml with tolerance for 1.0 mg AS and an SDL of >1.4 ng/ml with sensitivity to 1.0 mg AS or less constituted concordant responses. An SDL of <1.5 ng/ml with intolerance for 1.0 mg or less AS and an SDL of >1.4 ng/ml with tolerance for 1.0 mg AS comprised discordant responses. In 60 of 144 (42%) AS titrations discordant results were observed. Severe pulmonic, coronary, and aortic valvular heart disease, as well as old age, contributed to unusual AS sensitivitv. Titration with AS clarified pharmacologic quantification of SDL by providing insight into optimum therapeutic glycoside dose. Development of a radioimmunoassay for digoxin promised to resolve questions concerning appropriate dosage of this commonly employed digitalis glycoside. Several studies indicated that the quantity of drug present in the serum could be determined with precision. 9 Serum digoxin concentration measurements delineated a therapeutic range of values and provided a convenient marker for differentiating toxic from nontoxic patients with cardiac arrhythmias.20' 21 Eighty-five percent of patients with manifestations suggesting digitalis intoxication showed blood levels above 2.0 ng/ml; while a similar percentage of those without evidence of overdosage had concentrations below this value.22 However, the range of overlap between toxic and nontoxic groups was wide, from 1.6-3.0 ng/ml.22 More recent reports indicate an even wider range of overlap, extending through virtually the entire serum digoxin concentration span encountered clinically.23Implicit in the clinical use of serum digoxin levels for assessing the state of digitalization are two assumptions: first, that blood levels reflect faithfully myocardial drug concentrations, and second, that a given concentration is associated with specific effect.

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