Propafenone disposition kinetics in cardiac arrhythmia

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Cardiology

Background:

• Ventricular arrhythmias require effective antiarrhythmic drug therapy.
• Propafenone is a commonly used antiarrhythmic medication.
• Understanding drug disposition is crucial for optimizing patient treatment.

Purpose of the Study:

• To characterize the disposition kinetics of propafenone.
• To evaluate propafenone's pharmacokinetic behavior after intravenous and oral administration.
• To assess potential changes in propafenone kinetics during chronic oral dosing.

Main Methods:

• Pharmacokinetic study involving intravenous and oral administration of propafenone.
• Plasma concentration-time data analyzed using compartmental modeling (two- and three-compartment models).
• Calculation of key pharmacokinetic parameters including clearance, volume of distribution, and half-life.

Main Results:

• Propafenone disposition followed two-compartment kinetics in most patients.
• Model-independent parameters: clearance (11.2 mL/min/kg), steady-state volume of distribution (3.6 L/kg), and terminal half-life (5.0 hr).
• Elimination half-life increased to 6.2 hr after 5 days of oral dosing, with bioavailability exceeding 100%.

Conclusions:

• Propafenone disposition kinetics exhibit significant intersubject variability.
• Chronic oral propafenone administration may lead to decreased clearance and prolonged half-life.
• Findings suggest a potential need for dose adjustment during long-term propafenone therapy.