The effects of acute focal cerebral ischemia on digoxin toxicity and pharmacokinetics.

24 h after ligation of the left middle cerebral artery in cats (sham operation in the control group), a constant intravenous infusion of digoxin was begun and continued to toxicity (ventricular rhythm) and death. We found that the lethal dose of digoxin was significantly less in the stroke group than in the control group, but the lethal plasma digoxin concentration was significantly greater in the stroke group than in the control group. In a subsequent study, we demonstrated that ischemic stroke caused a significant prolongation in the elimination half-life of digoxin and an increase in the volume of distribution. The mean plasma clearance of the stroke group was approximately three fourths of that of the control group. We concluded that the decreased tolerance to digoxin after ischemic stroke was due to the prolonged half-life and decreased clearance of digoxin.