Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis

The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3 +/- 4.8 h (+/- SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5 +/- 4.6 h, which was calculated to correspond to removal of 25 +/- 14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10-55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2 +/- 4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.