Evaluation of a Sex‐Based Difference in the Pharmacokinetics of Digoxin

Study Objective. To determine whether a sex‐based difference in digoxin pharmacokinetics exists in patients receiving long‐term digoxin therapy for chronic heart failure or atrial fibrillation. Design. Single‐center, retrospective review of medical records. Setting. University‐based teaching hospital and outpatient clinic. Patients. Sixty‐seven adults (32 men, 35 women) with chronic heart failure or atrial fibrillation who were receiving digoxin therapy. Measurements and Main Results. Serum digoxin concentrations and daily digoxin doses were obtained from patients' medical records. Daily doses were adjusted for patients' actual and ideal body weight and body mass index (BMI). The ratio between the serum digoxin concentration and each of the adjusted daily doses of digoxin was compared between men and women. The mean ± SD serum digoxin concentration was 0.85 ± 0.51 ng/ml for men compared with 1.02 ± 0.51 ng/ml for women. Mean ± SD unadjusted doses of digoxin were 0.180 ± 0.063 and 0.164 ± 0.059 mg/day for men and women, respectively; the difference was not statistically significant. Ratios of serum digoxin concentration to daily digoxin doses did not differ by sex when doses were estimated with actual or ideal weight. Only the ratio of the digoxin concentration to the BMI‐adjusted dose was significantly different between men and women (0.14 ± 0.09 and 0.19 ± 0.11, respectively, p<0.05). Conclusion. Sex‐based differences in digoxin pharmacokinetics were absent when actual or ideal body weight was used. However, the ratio of serum digoxin concentration to daily digoxin dose adjusted for BMI differed by sex. Because digoxin is distributed to lean body mass, use of the BMI could have overadjusted body weight, leading to inaccurate pharmacokinetic assumptions and calculations. The pharmacokinetics of digoxin do not appear to differ by sex.