Interindividual differences in the pharmacokinetics of digitoxin and digoxin during long-term treatment

Patients suffering from congestive heart failure received maintenance doses of digitoxin (N = 10) or digoxin (N = 8). The plasma glycoside concentration was determined, and after a single dose of 3H-digitoxin or 3H-digoxin, the decline and excretion of radioactivity were measured over a period of 7 (digitoxin) and 3 days (digoxin). Plasma radioactivity declined with a T1/2 beta between 77 and 234 h (mean 138 h) in the case of digitoxin and with a T1/2 beta between 9.2 and 38.6 h (mean 23.5 h) for digoxin. A close correlation between T1/2 beta and excreted radioactivity and T1/2 beta and total plasma level was found for digitoxin. In 4 patients TLC of urine showed that interindividual variations in digitoxin elimination could possibly be attributed to variation in metabolism, resulting in the production of different metabolites. Predicted digitoxin plasma levels agreed well with measured values. The maintenance dose could be calculated from the total body clearance (VCl) and a presumed plasma glycoside level. The recommended technique facilitates dosage calculations in patients treated with digitoxin.