The clinically relevant interaction between quinidine (3 mg/kg) and digoxin (0.6 mg/kg plus 20 μCi 3H-digoxin) was investigated using unanesthetized and unrestrained guinea pigs for in vivo pharmacokinetic and tissue disposition studies. Quinidine caused a significant elevation of plasma levels of digoxin as early as 5 min after injection, and the increase persisted for at least 8 h. A significant decrease in the volume of distribution for digoxin from 3.6 to 2.7 liters/kg (20%) was observed in quinidine-treated animals. No change was noted in the dominant elimination half-life of digoxin in quinidine-treated animals. The decreased volume of distribution appeared to be due to displacement of digoxin from tissue stores by quinidine as evidenced by decreased tissue to plasma ratios for kidney (41%), intestine (41%), fat (33%), lung (31%), left ventricle (27%), liver (24%), left atrium (22%), right ventricle (21%), right atrium (18%), pancreas (12%), and bladder (-4%) samples.
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