Key result
Inhaled flecainide undergoes Phase 1 PK and PD evaluation versus IV infusion in healthy adults.
Why the study?
The relationship between pharmacokinetics and pharmacodynamics of flecainide delivered via oral inhalation compared to IV infusion was not established.
Inhaled flecainide exhibits PK-PD hysteresis versus IV; leaves open whether this alters safety or efficacy in acute AF patients.
Background: The class IC antiarrhythmic agent flecainide is being developed for delivery via oral inhalation for the management of acute episodes of recent onset atrial fibrillation. Widening of the QRS complex is a known pharmacodynamic effect of flecainide. Purpose: Data from a recently completed Phase 1 study were analyzed to determine whether the relationship between the pharmacokinetics (PK) and the pharmacodynamics (PD), measured by changes in QRS, of flecainide delivered by oral inhalation are similar to those when delivered via IV infusion. Methods: This Phase 1 study in 6 healthy volunteers was carried out to assess the PK and PD of flecainide delivered via IV infusion over 10 minutes (2 mg/kg, ∼ 150 mg) vs. oral inhalation delivered over 4.5 minutes (estimated total lung dose, eTLD of 30 mg) using a 2-period crossover design study. Oral inhalation was performed using a hand-held inhaler (Trudell AeroEclipse II BAN). Venous plasma samples were drawn and ECGs were recorded at various times pre-, during and post-dosing.
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Madhavapeddi et al. (2018) studied Healthy volunteers (n=6). Flecainide via oral inhalation vs. Flecainide via IV infusion (2 mg/kg, ~150 mg over 10 minutes) was evaluated on Relationship between pharmacokinetics and pharmacodynamics (measured by changes in QRS duration).
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