Dose-response relation between therapeutic levels of serum digoxin and systolic time intervals

Abstract

A dose-response relation between cardiac glycosides and systolic time intervals has previously been established in short-term studies in which the glycoside was administered intravenously. In these studies there was uncertainty regarding the steady state kinetics, and maintenance of the early serum levels would have resulted in toxicity. Accordingly, we studied the effect on systolic time intervals of small increments of serum digoxin within the therapeutic range. Serum digoxin concentration and systolic time intervals were measured in 21 patients receiving 0.25 mg of the glycoside daily. The daily dose was increased to 0.5 mg and measurements were repeated 5 to 7 days later. Serum digoxin concentration with the smaller dose was 0.56 ± (standard error) 0.06 ng/ml and increased to 1.18 ± 0.11 ng/ml with the larger dose. Associated with the increased serum digoxin was a mean decrease in duration of total electromechanical events of 6.3 ± 2.9 msec ( P < 0.025), which resulted from a mean shortening of left ventricular ejection time of 5.6 ± 3.0 msec ( P < 0.05). The mean decrease in preejection phase of 1.1 ± 2.1 msec was insignificant ( P > 0.2). Repeated measurements in control patients showed no change in serum digoxin concentration or systolic time intervals. In nine patients the digoxin dose was randomly varied between 0 and 0.75 mg and measurements were made 4 to 5 days after drug administration at each dose level. The correlation coefficient between changes in serum digoxin and changes in left ventricular ejection time was −0.55 ( P < 0.01) The data indicated that increasing the maintenance dose of digoxin while keeping the serum level within therapeutic range will result in improved ventricular function as assessed by determination of systolic time intervals.