The pharmacokinetics of disopyramide and mono-N-dealkyl-disopyramide in humans.
The pharmacokinetics of disopyramide and its metabolite mono-N-dealkyl-disopyramide (MND) were studied after a single oral and intramuscular dose and at steady state in healthy volunteers, after an intravenous dose in post-surgery patients, and after a single oral dose in two 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 from 0.58 to nearly 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 from 4.4 to 17.1 in post-surgery patients, and those of the renal patients were 10.6 and 8.7 h.
D000284:Administration, Oral; D000328:Adult; D004206:Disopyramide / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011725:Pyridines / Q000378:metabolism*
D011725:Pyridines; C030438:4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide; D004206:Disopyramide