Digoxin-Quinidine Interaction in the Neonatal Dog
The effects of quinidine on steady state serum and tissue digoxin concentrations in the neonatal dog were studied. To determine the effects of quinidine on serum digoxin concentrations, two groups of neonates were evaluated: Group I (n = 11) was digitalized with 40 μg/kg body weight, intramuscularly, and placed on a 10 μg/kg per day maintenance dose; Group II (n = 7) was digitalized with 50 μg/kg per day, intraperitoneally, and placed on a 20 μg/kg per day maintenance dose. After 10 days of digoxin alone, quinidine was coadministered (30 mg/kg per day, intraperitoneally) for 7 days. Serum digoxin concentrations were measured before quinidine and 1, 3 and 7 days after combined digoxin-quinidine therapy. In Group I, the control serum digoxin concentration was 1.38 ± 0.32 ng/ml and after 7 days of combined therapy it was unchanged (1.39 ± 0.31 ng/ml). In Group II, the control serum digoxin concentration measured 2.80 ± 0.49 ng/ml and after 7 days of combined therapy it, too, was unchanged (3.10 ± 0.65 ng/ml). The effects of combined digoxin-quinidine administration on tissue digoxin concentrations were studied in two other groups of neonates. Group III (n = 6) was given a low maintenance dose of digoxin (10 ng/kg per day, intramuscularly) and a full 7 days of coadministered quinidine; in Group IV (n = 6), digoxin was given at a higher dose (20 μg/kg per day, intraperitoneally) and a shorter duration of combined digoxin-quinidine therapy (3 days). Tissue samples of skeletal muscle, brain, myocardium, liver and kidney were analyzed for digoxin content and compared with tissue levels measured in control neonates given digoxin alone. Brain digoxin concentrations were higher in Group IV (910 ± 437 ng/g) compared with neonates given digoxin alone (530 ± 49 ng/g). In both Groups III and IV, digoxin tissue concentrations in skeletal muscle, liver and brain, normalized for the serum digoxin level, were significantly higher than in control neonates. In the neonatal dog, quinidine administration results in little or no increase in the steady state serum digoxin concentration. However, quinidine may be associated with higher brain digoxin levels, particularly at higher digoxin doses and serum levels. © 1986, American College of Cardiology Foundation. All rights reserved.
& Gelband, H.
(1986). Digoxin-Quinidine Interaction in the Neonatal Dog. Journal of the American College of Cardiology, 8 (3), 669-674.