Effect of physical exercise on the pharmacokinetics of digoxin during maintenance treatment

Blood samples were taken repeatedly and urine was collected for digoxin assays on two occasions from 12 healthy male volunteers after an oral maintenance dose of digoxin. On one occasion the subjects exercised intermittently on a bicycle ergometer for 8 h after the dose. On the other occasion they rested in the supine position during the study period. Thirty and 45 min after the intake of digoxin, the serum digoxin concentration was significantly higher during exercise compared with rest, indicating increased absorption rate during exercise. Two and 4 h after the intake of digoxin, the serum digoxin concentration was significantly lower during exercise than during rest. Furthermore, the intermittent bicycle exercise decreased the renal excretion of digoxin during the study period. It also increased the steady state digoxin concentration measured after a terminating standardized period of rest. The most probable reason for these changes in the pharmacokinetics is a previously described increased binding of digoxin to exercising muscles. According to the results, there is reason to believe that the daily physical activity performed by digoxin-treated patients will determine to some extent the body content of digoxin. Changes in activity from day to day may therefore cause variations in the effect of the drug.