Digoxin-quinidine interaction in patients with chronic renal failure.

Abstract

SUMMARY We evaluated the effect of quinidine on digoxin pharmacokinetics in six patients with severe renal failure. Quinidine reduced the total body clearance of digoxin from 1.87 to 1.06 1/hour (p < 0.001), and prolonged the digoxin half-life of elimination from 5.20 to 9.61 days (p < 0.01). The digoxin volume of distribution was unchanged. Renal clearance of digoxin was negligible; thus, the decrease in total body clearance was due to a decrease in the nonrenal clearance of digoxin. The mean trough serum concentrations of quinidine ranged from 1.0 to 3.0 ,ug/ml. We conclude that in patients with chronic renal failure, the dose of digoxin should be decreased by 50% if quinidine therapy is initiated.QUINIDINE increases digoxin serum concentrations approximately twofold.' This elevation in concentration occurs primarily as a result of a decrease in the total body clearance of digoxin and volume of distribution of digoxin.2 A decrease in digoxin nonrenal clearance has also been reported.3 However, the magnitude of the change in nonrenal clearance has varied widely.3 '-6 In renal failure patients, the renal clearance of digoxin is small relative to the nonrenal clearance. If the quinidine effect on digoxin nonrenal clearance is small, then in patients with chronic renal failure, quinidine may induce only a small change in digoxin total body clearance. In addition, these patients demonstrate a decreased digoxin volume of distribution7 due to decreased tissue binding of digoxin.8 Whether quinidine alters this already decreased digoxin volume of distribution is not known. We therefore evaluated the effect of quinidine on digoxin kinetics in chronic dialysis patients to assess the effects of renal failure on this drug interaction and to gain further insight into the mechanisms of this interaction. Methods PatientsSix adults gave informed, written consent to participate in the study, which was approved by the Human Subjects Committee of the Arizona Health Sciences Center. The clinical characteristics of the subjects are listed in table 1. All subjects had end-stage renal disease. Five subjects were on chronic hemodialysis; one (subject 5) was on continuous ambulatory peritoneal dialysis during the first half of the study and hemodialysis during the second half. Five patients were males and one was female, ages 30-58 years (mean 47 years). Serum creatinine levels ranged from 10.2 to 16.8 mg% (mean 13.4 mg%). No subject was on digoxin or quinidine or any drug known to affect the pharmacokinetics of intravenously administered digoxin at the time of enrollment. ProtocolSubjects were given quinidine gluconate, 324-mg tablets containing 202 mg of quinidine, twice daily. After 3 days of quinidine, a single dose of digoxin, 0. 6 or 0.8 mg, was administered intravenously over 10 minutes. Blood samples were obtained 0.5, 1, 2, 4, 6 and 8 hours, and once on days 2, 3,4,7,9,11, 14, 16, 18, 21, and 23 after the digoxin dose. The blood samples were drawn immediately before a quinidine dose on these days. Quinidine was then discont...

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