Changes in Steady State Digoxin Pharmacokinetics during Quinidine Therapy in Cardiac Patients: Influence of Plasma Quinidine Concentration

: In seven cardiac patients on long-term digoxin therapy, digoxin kinetics were investigated — in the absence and presence of quinidine — after simultaneous administration of an oral digoxin dose and an intravenous 3H-digoxin bolus injection. From 3H-digoxin data quinidine was found to decrease both renal (from 1.19 ±0.35 to 0.86 ±0.21 ml/min./kg) (P<0.02) and extrarenal clearances of digoxin (from 0.85 ±0.24 to 0.49±0.23 ml/min./kg) (P<0.02), and to diminish the steady state distribution volume of the drug (from 6.78 ± 1.23 to 5.63 ± 1.64 l/kg) (P<0.02). Plasma half-life increased from 51.5 ±5.4 to 64.4±14.8 hrs (P<0.05), while urinary excretion half-life increased from 54.4±3.9 to 78.5± 14.1 hrs (P<0.01). Pharmacokinetic parameters derived from plasma and urinary digoxin data showed similar changes during quinidine therapy. Reduction in renal 3H-digoxin clearance occurred at subtherapeutic plasma quinidine levels and was independent of plasma quinidine, whereas reductions in extrarenal 3H-digoxin clearance and 3H-digoxin distribution volume were positively correlated to plasma quinidine concentrations (P<0.05).