Influence of concentration-dependent protein binding on serum concentrations and urinary excretion of disopyramide and its metabolite following oral administration.

Concentrations of disopyramide (D) and mono-N-dealkyldisopyramide (MND) were measured in serum and urine following administration of 100, 150, 200, and 300 mg D to four volunteers. The free fraction of D in serum was drug concentration-dependent in all four subjects following the administration of the four doses. Areas under the free (unbound) D serum concentration-time curves (AUC free 0-9) were linearly related to dose following 100-200 mg D. AUC free 0-9 values were 30-60 per cent higher than expected in two subjects following 300 mg D due to an apparent dose-dependent decrease in D renal tubular secretion. Renal clearance of free D averaged 10.9 1 h-1. The renal clearance of MND averaged 10.3 1 h-1. The urinary excretion of MND was proportional to disopyramide dose.