Disopyramide concentrations in saliva

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Clinical Pharmacology

Background:

• Disopyramide is an antiarrhythmic drug with variable absorption and metabolism.
• Understanding drug concentrations in different bodily fluids is crucial for therapeutic drug monitoring.
• Saliva offers a non-invasive alternative for drug level assessment, but its reliability needs validation.

Purpose of the Study:

• To investigate the relationship between saliva and plasma concentrations of disopyramide and its metabolite, mono-N-dealkyldisopyramide.
• To assess the protein binding of disopyramide and its impact on salivary concentrations.
• To determine the reliability of salivary disopyramide levels for predicting plasma concentrations.

Main Methods:

• Ten healthy volunteers received a single oral dose of 400 mg disopyramide.
• Saliva and plasma samples were collected at various time points.
• Concentrations of disopyramide, its metabolite, and plasma protein binding were measured.
• Salivary flow rate and pH were also recorded.

Main Results:

• Disopyramide exhibited a concentration-dependent inhibition of salivary flow rate.
• Good correlations were observed between salivary and plasma concentrations of disopyramide and its metabolite.
• The unbound fraction of disopyramide in plasma varied significantly between individuals.
• Saliva-to-plasma (S/P) ratios were highest at peak drug concentrations.
• No significant correlation was found between S/P ratio and salivary pH.

Conclusions:

• Salivary disopyramide concentrations are not reliable predictors of total or free plasma concentrations.
• Significant interindividual variability exists in disopyramide pharmacokinetics.
• Non-invasive monitoring of disopyramide via saliva may be limited due to poor predictive value.