Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions

Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin pharmacokinetics is still controversial because most studies were not performed with subjects achieving definite steady-state conditions. To determine whether quinidine affects digitoxin kinetics and cardiac efficacy, we measured glycoside plasma concentrations and renal excretion as well as ECG parameters and systolic time intervals before and during quinidine dosing in eight healthy subjects at steady state. Mean (+/- SD) digitoxin plasma concentrations and renal excretion increased from 13.6 +/- 2.2 ng/ml and 16.1 +/- 5.8 micrograms/24 hours before dosing to 19.7 +/- 3.1 ng/ml and 23.4 +/- 4.9 micrograms/24 hours, respectively, during quinidine dosing for 32 days. While renal digitoxin clearance was not noticeably changed by quinidine, total digitoxin clearance and extrarenal digitoxin clearance decreased by an average of 32% and 40.5%, respectively. The elimination t1/2 was prolonged from 150.3 +/- 20.6 to 202.6 +/- 37.5 hours. The increased digitoxin plasma level is pharmacodynamically active. We conclude that there is a clinically important interaction between digitoxin and quinidine, but it is to a lesser extent and is caused by different mechanism, in part, than the interaction between digoxin and quinidine.