THE PHARMACOKINETICS OF DISOPYRAMIDE AND MONO-N-DEALKYL-DISOPYRAMIDE IN HUMANS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 20  (5) , 219-226
Abstract
The pharmacokinetics of disopyramide and its metabolite mono-N-dealkyldisopyramide (MND) were studied after a single oral and i.m. dose and at steady state in healthy volunteers, after an i.v. dose in postsurgery patients, and after a single oral dose in 2 patients with renal insufficiency. After an oral dose in healthy volunteers the plasma elimination half-life of total disopyramide was 8.65 .+-. 1.37 h, and that of the non-protein-bound disopyramide, 4.74 .+-. 1.20 h. The protein binding of disopyramide varied at 0.58-1.0, and was concentration dependent. All subjects had detectable amounts of MND in plasma. Its elimination half-life was 12.9 .+-. 6.43 h. The ratio of MND to disopyramide was 0.23 .+-. 0.09 in plasma and 0.46 .+-. 0.11 in urine. There was a close correlation (r = 0.868) between the renal clearances of free disopyramide and creatinine. The renal clearances of disopyramide (both free and total), MND and creatinine varied with time; this resembled variation in the urine flow. The kinetics of one dose at steady state did not differ markedly from that of a single dose. The elimination half-lives of total disopyramide varied at 4.4-17.1 h in postsurgery patients, and those of the renal patients were 10.6 and 8.7 h.