Comparative bioavailability study of three sustained release quinidine formulations

Area of Science:

• Pharmacokinetics
• Drug Absorption
• Clinical Pharmacology

Background:

• Sustained-release formulations aim to provide consistent drug levels.
• Quinidine is an antiarrhythmic agent requiring careful dose management.
• Understanding absorption differences between formulations is crucial for therapeutic efficacy.

Purpose of the Study:

• To compare the absorption characteristics of three different sustained-release quinidine formulations.
• To evaluate peak concentrations, absorption rates, and steady-state trough levels.
• To determine if absorption models (zero-order vs. first-order) differ between formulations.

Main Methods:

• A randomized, 3-way crossover trial involving 12 healthy male volunteers.
• Administration of single tablets of Quinidex (300mg), Biquin Durules (250mg), and Quinaglute Dura-Tabs (324mg) every 12 hours for 5 days.
• Measurement of quinidine serum concentrations and analysis using pharmacokinetic parameters and Wagner-Nelson plots.

Main Results:

• Peak quinidine serum concentrations were significantly higher for Quinaglute compared to Biquin and Quinidex.
• The extent of absorption (AUC infinity) was similar across all three formulations.
• Quinidex exhibited significantly greater mean steady-state trough concentrations and a much slower absorption rate compared to Biquin and Quinaglute.

Conclusions:

• While the overall extent of absorption is comparable, significant differences exist in the rate and peak concentrations of these sustained-release quinidine formulations.
• Quinidex demonstrates slower absorption and higher trough levels, suggesting potential for prolonged absorption beyond the 12-hour dosing interval.
• These pharmacokinetic variations necessitate careful consideration when selecting a sustained-release quinidine product for patient therapy.