Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: class Ic antiarrhythmic drug, ATC code: C01BC04 
Flecainide acetate is a class Ic antiarrhythmic drug with negative inotropic effect. It binds to the sodium channels of the muscle membranes and results in a considerable decrease in cardiac excitation conduction speed and suppression of spontaneous premature ventricular complexes. In the myocardium, flecainide acetate binds heavily to fast sodium channels and thus slows the depolarisation speed; conduction in the atrium, AV node, ventricle and Purkinje fibres is reduced. The most pronounced effect is seen in the Purkinje fibres.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Distribution volume: 8.7 L/kg BW pKa value: 9.3
In general, steady state conditions are reached after approximately 4 days (equivalent to approximately 5 half-lives). In patients with dose restrictions (see section 4.2), the altered flecainide metabolism and elimination rate can mean that it takes 6–8 days or in extreme cases even up to 20 days for steady state to be reached.

The average plasma half-life in patients with heart disease is around 20 hours. The vast majority of patients who were successfully treated with flecainide had plasma levels of 200– 1 000 ng/mL, depending on the selected dose. In a period of 12 hours without administration of the drug, the flecainide plasma level decreases by 25–30%.
Flecainide does not experience any noteworthy first pass effect in the liver but does undergo significant secondary metabolism. The metabolites found to date show no or very little antiarrhythmic effect and according to current findings do not cause any adverse reactions.
Flecainide and the metabolites found to date (including conjugated compounds) are almost completely eliminated through the kidneys; only 5% flecainide and metabolites were found in the faeces.

Investigations have found that flecainide elimination is dependent on urine pH. With a urine pH of 4.4–5.4, approximately 45% of a single flecainide dose is eliminated unchanged by the kidneys within 32 hours; with a urine pH of 7.4–8.3, the elimination rate of non-metabolised flecainide is 7.4%.
For interaction with other substances, see section 4.5.

The plasma protein binding of flecainide is 32–47% and is not affected by the dose administered or the flecainide plasma level. The free flecainide plasma level shows a close correlation with the dose administered.