Potent Inhibition of Cytochrome P450IID6 (Debrisoquin 4‐Hydroxylase) by Flecainide In Vitro and In Vivo

  title={Potent Inhibition of Cytochrome P450IID6 (Debrisoquin 4‐Hydroxylase) by Flecainide In Vitro and In Vivo},
  author={Walter Emil Haefeli and Mario J. Bargetzi and Ferenc Follath and Urs A. Meyer},
  journal={Journal of Cardiovascular Pharmacology},
Flecainide acetate, a class Ic antiarrhythmic agent, is eliminated to a larger extent by renal excretion and to a minor extent by the liver. In patients with impaired renal function or with elevated urinary pH, however, its elimination is dominated by hepatic metabolism. Recent evidence suggests that the in vivo metabolism of flecainide is controlled by the genetic polymorphism of the debrisoquin/sparteine type; i.e., it is a substrate of cytochrome P4501ID6. We investigated the inhibitory… 

Pharmacogenetics: Part II

A single isozyme of the cytochrome P-450 (CYP) family, designated CYPIID6, is responsible for the metabolism of debrisoquin-type substrates. A cDNA containing the full protein coding sequence for

Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry

The intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare, and more clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype.

Polymorphism of Human Cytochrome P450 2D6 and Its Clinical Significance

There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population and the number of alleles is still growing.

P450 Enzymes

The use of human hepatocyte preparations in culture is a promising new direction that could assist the determination of modifications to drug therapy necessitated by exposure to inducing agents, however, the use of drugs known to increase the microsomal expression of particular P450s, and increase associated drug oxidation capacity in humans, should be used with caution.

Clinical implications of the competitive inhibition of the debrisoquin-metabolizing isozyme by quinidine.

Clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications because no test is commonly available to determine directly the debrisoquin metabolic phenotype.

The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers

It is suggested that quinidine inhibits the first step of flecainide metabolism, although it may also reduce its renal clearance, but to a lesser extent.

The Consequences of 3,4-Methylenedioxymethamphetamine Induced CYP2D6 Inhibition in Humans

A controlled clinical trial was conducted in 15 healthy male subjects whereby a probe drug, dextromethorphan (DEX), was administered after an oral dose of 1.5 mg/kg MDMA to evaluate changes in CYP2D6 activity.

Bio-analytical method development and validation of Flecainide by Liquid-liquid extraction with LC-MS / MS : by application to a pharmacokinetic study

  • Medicine, Biology
  • 2017
It has high bioavailability after an oral dose with plasma half-life is about 20 hours with Peak serum concentrations can be seen 1 to 6 hours after ingestion of an oral dose. [1-2]. During oral