Plasma and saliva propafenone concentrations at steady state

Area of Science:

• Pharmacokinetics
• Drug Metabolism and Disposition
• Clinical Pharmacology

Background:

• Propafenone is an antiarrhythmic drug with variable patient responses.
• Understanding propafenone's pharmacokinetic variability is crucial for optimizing therapeutic outcomes.
• Saliva sampling offers a non-invasive alternative for drug monitoring.

Purpose of the Study:

• To characterize the pharmacokinetic variability of propafenone in healthy male subjects.
• To assess the correlation between plasma and saliva propafenone concentrations at steady state.
• To determine key pharmacokinetic parameters including elimination half-life and steady-state concentrations.

Main Methods:

• Administered 300 mg propafenone every 8 hours for 6 days in two phases.
• Collected plasma and saliva samples during approach to steady state and at steady state.
• Assayed propafenone concentrations using high-performance liquid chromatography (HPLC).

Main Results:

• Observed significant intersubject variability in elimination half-life (2.1-27.2 h) and mean steady-state plasma concentrations (0.3-3.03 microgram/mL).
• Demonstrated low intrasubject variability, indicating consistent kinetics within individuals across study phases.
• Found saliva propafenone concentrations to be 24.7% +/- 11.1% of plasma concentrations, with a significant positive correlation between steady-state plasma and saliva levels (p < 0.001).

Conclusions:

• Propafenone exhibits substantial intersubject pharmacokinetic variability, necessitating individualized dosing strategies.
• Saliva propafenone measurements are a reliable, non-invasive surrogate for plasma concentrations, supporting its use in therapeutic drug monitoring.
• The consistent intrasubject kinetics suggest predictable drug behavior within individuals once steady state is achieved.