DISOPYRAMIDE CONCENTRATIONS IN SALIVA

Abstract

The saliva and plasma concentrations of disopyramide [a cardiovascular drug] and its main metabolite, mono-N-dealkyldisopyramide, and the protein binding of disopyramide were studied in 10 healthy volunteers after a single oral 400-mg dose of disopyramide. Disopyramide had a concentration-dependent inhibitory effect on the salivary flow rate. The correlations between the salivary and total plasma concentrations of disopyramide (r = 0.774 linear, 0.890 exponential, P < 0.001), of the metabolite (r = 0.700, P < 0.001), and between the salivary and free plasma concentrations of disopyramide (r = 0.785, P < 0.001) were relatively good. The fraction of disopyramide not bound to plasma proteins varied from not measurable to 0.35, was concentration-dependent and showed intersubject variation. The ratio of disopyramide concentrations in saliva and plasma (S/P ratio) varied from 0.08-1.51 and was highest when the salivary and plasma levels were high. No significant correlation existed between S/P ratio and salivary pH, and the correlation was poor (r = 0.546) between the measured salivary concentrations and those calculated theoretically. A wide interindividual variation was seen in all parameters measured. The salivary concentrations of disopyramide are unreliable for predicting the corresponding total or free plasma concentrations.