Pharmacodynamic variability of flecainide assessed by QRS changes

  title={Pharmacodynamic variability of flecainide assessed by QRS changes},
  author={Roberto Padrini and Donatella Piovan and M. Busa and Muhamad AL‐BUNNI and Piera Maiolino and Mariano Ferrari},
  journal={Clinical Pharmacology \& Therapeutics},
The effect of flecainide on the QRS interval was studied in 10 patients who were receiving long‐term oral treatment (50 to 150 mg twice daily) for arrhythmias that were refractory to other drugs. Total and free drug plasma levels and QRS durations were measured at intervals after the morning administration. Free drug plasma levels were linearly correlated with QRS duration in each patient and the slope of the line was widely variable in the population studied. Even after the data from one… 

Assessment of serum flecainide trough levels in patients with tachyarrhythmia

It is concluded that to control paroxysm in patients receiving flecainide for tachyarrhythmia serum flecainside concentrations should be maintained at ≥ 300 ng mL−1.

Absorption kinetics and pharmacodynamics of two oral dosage forms of flecainide in patients with an episode of paroxysmal atrial fibrillation

The probability of cardioversion after an oral loading dose of flecainide in patients with AF is dependent on ka and rapid loading of the effect compartment, i.e. the atria, appears to be critical to reach cardioversion.

Effect of Flecainide on Heart Rate Variability in Subjects Without Coronary Artery Disease or Congestive Heart Failure

It was concluded that in subjects without coronary artery disease or congestive heart failure, flecainide decreases all the measurements of heart rate variability and this decrease is not related to plasma concentrations of fleCainide.

Predicting Effective Drug Concentrations for Individual Patients

  • G. Levy
  • Biology, Medicine
    Clinical pharmacokinetics
  • 1998
Correction of drug concentrations in plasma for protein binding, consideration of active and interactive metabolites, stereospecific assays and attention to drug distribution disequilibria are essential for successful identification of factors affecting pharmacodynamic variability.

Impact of pharmacodynamic variability on drug delivery(1).

  • Levy
  • Biology, Medicine
    Advanced drug delivery reviews
  • 1998

Antiarrhythmic drug initiation in patients with atrial fibrillation.

Extracorporeal Circulatory Support in Near-Fatal Flecainide Overdose

The case of a 20-year-old female who took approximately 4 grams of flecainide and a small amount of paracetamol as an impulsive gesture is reported, believed to be the first reported case of fle cainide overdose, requiring extracorporeal circulatory support, not resulting in neurological deficit.



Pharmacodynamics and side effects of flecainide acetate

The risk of cardiovascular side effects increases at higher plasma levels of flecainide and is associated with greater increases in the PR and QRS intervals from baseline than are routinely observed during flecainside dosing.

Metabolism of flecainide.

Total suppression of ventricular arrhythmias by encainide. Pharmacokinetic and electrocardiographic characteristics.

Encainide was a highly effective, well-tolerated antiarrhythmic agent and a single patient whose arrhythmia and electrocardiogram were unchanged during therapy eliminated the drug much more slowly than the others and was the only patient in whom no O-demethyl form could be detected in plasma, suggesting that this metabolite may be active.

Plasma and tissue levels of flecainide in rats.

Relationship between use-dependent effects of antiarrhythmic drugs on conduction and Vmax in canine cardiac Purkinje fibers.

  • S. Nattel
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1987
The experiments show that local anesthetic drugs produce use dependent changes in conduction time in vitro with time constants comparable to simultaneously measured time constants for effects on Vmax, implying that the use dependence of drug effects on cardiac conduction can be studied quantitatively in vivo by studying the response to changes in activation frequency.

Interval-dependent effects of lidocaine on conduction in canine cardiac Purkinje fibers: experimental observations and theoretical analysis.

  • S. Nattel
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1987
The observations suggest that the time dependence of drug effects on conduction in vivo can be analyzed quantitatively in relationship to observations on Vmax in vitro, and calculations using this model suggest that recovery from moderate drug-induced conduction slowing should proceed with a time course similar to changes in Vmax.

Upregulation of the rat cardiac sodium channel by in vivo treatment with a class I antiarrhythmic drug.

In vivo administration of the class I antiarrhythmic drug mexiletine to rats induces sodium channel upregulation in isolated cardiac myocytes, and the number of sodium channels returned to normal within 12 d.

Interactions of flecainide with guinea pig cardiac sodium channels. Importance of activation unblocking to the voltage dependence of recovery.

The results indicate that flecainide has a low affinity for rested (R) and inactivated (I) channels but a high affinity for activated ones (A) while unblocking occurs via two separate pathways: activated and closed states.

Antiarrhythmic drug action. Blockade of the inward sodium current.

The mechanism of the blockade of the sodium current is focused on, which is probably a major mechanism of action of antiarrhythmic drugs.