Genetically‐determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect.
Key result
Low-dose quinidine increased mean steady-state plasma propafenone concentrations from 408 to 1096 ng/ml (P<0.001) in extensive metabolizers, without altering ECG intervals or arrhythmia frequency.
Why the study?
Does low dose quinidine alter the pharmacokinetics and pharmacodynamics of propafenone in patients with ventricular arrhythmias based on their metabolizer phenotype?
Population
9 patients receiving propafenone for the treatment of ventricular arrhythmias
Comparison
Coadministration of low dose quinidine vs Baseline
Design
Cohort
Authors
Discussion
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Implication
PK interaction may not alter propafenone's clinical effects in extensive metabolizers; hypothesis-generating for metabolite compensation.
Structured PICO
Does low dose quinidine alter the pharmacokinetics and pharmacodynamics of propafenone in patients with ventricular arrhythmias based on their metabolizer phenotype?
P
Population
9 patients (7 extensive and 2 poor metabolizers) receiving propafenone for the treatment of ventricular arrhythmias.
I
Intervention
Coadministration of low dose quinidine
C
Comparator
Baseline (propafenone therapy alone prior to quinidine coadministration)
O
Outcome
Steady-state plasma propafenone and 5-hydroxypropafenone concentrations, and propafenone oral clearancesurrogate
Main Result
Absolute Event Rate: 1096% vs 408%
p-value: p=<0.001
Low-dose quinidine significantly alters propafenone pharmacokinetics in extensive metabolizers without changing clinical antiarrhythmic effects, highlighting the compensatory role of active metabolites.
Cite This Study
Funck‐Brentano et al. (1989) studied Ventricular arrhythmias (n=9). Quinidine vs. Propafenone alone (baseline) was evaluated on Mean steady-state plasma propafenone concentrations in extensive metabolizers (p=<0.001). Low-dose quinidine increased mean steady-state plasma propafenone concentrations from 408 to 1096 ng/ml (P<0.001) in extensive metabolizers, without altering ECG intervals or arrhythmia frequency.