Effects of Coadministration of Propafenone on the Pharmacokinetics of Digoxin in Healthy Volunteer Subjects

Previous reports have suggested an interaction between propafenone and digoxin. We investigated the pharmacokinetics of IV digoxin when given alone (Phase I), after pretreatment with propafenone 150 mg every 8 hours for seven days (Phase II), and after propafenone 300 mg every 8 hours for 7 days (Phase III). The total body clearance of digoxin during Phase I was 2.45 ml/min/kg and was 2.17 ml/min/kg during Phase II (NS) and decreased to 1.92 ml/min/kg during Phase III (P < 0.05). The renal clearance and half‐life of digoxin were not significantly altered by propafenone. There was a trend towards a decrease in the volume of distribution of digoxin from 9.43 L/kg in Phase I, to 9.33 L/kg in Phase II, and 8.02 L/kg in Phase III. Similarly there was a trend towards a decreased nonrenal clearance of digoxin from 1.21 ml/min/kg during Phase I to 1.01 ml/min/kg during Phase II and to 0.75 ml/min/kg during Phase III. The changes in volume of distribution and nonrenal clearance parallel each other resulting in no change in the elimination half‐life of digoxin. It is postulated that the mechanism of this interaction is due to decreases in the volume of distribution and nonrenal elimination of digoxin by propafenone. The degree of this interaction was related to the dose of propafenone. The magnitude of this interaction may be greater in patients and, thus, may require a reduction in the digoxin dose. 1989 American College of Clinical Pharmacology