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Encainide metabolism

Encainide is almost completely absorbed from the GI tract. Eood may delay absorption without altering its bioavailabiUty. The dmg is rapidly metabolized in 90% of the patients to two principal metaboUtes, 0-demethylencainide (ODE) and 3-methoxy-O-demethylencainide (MODE), while the other 10% metabolize encainide slowly with Htde or no ODE or MODE formed. Encainide, ODE, and MODE are extensively protein bound 75—80% for encainide and ODE and 92% for MODE. Peak plasma concentrations are achieved in 30—90 min. Therapeutic plasma concentrations are very low the concentrations of ODE and MODE are approximately five times those of encainide. The findings with the metaboUtes are significant because ODE is 2—10 times and MODE, 1—4 times more effective than encainide as antiarrhythmics. The half-Hves for encainide in fast and slow metabolizers is 1—2 h and 6—12 h, respectively. The elimination half-life for ODE is 3—4 h and for MODE 6—12 h in fast metabolizers. Excretion occurs through the Hver and kidneys (1,2). [Pg.114]

Genetic polymorphism is clinically important e.g. in the CAST (Cardiac Arrhythmia Suppression Trial), serious problems were identified with encainide and flecainide, because of polymorphic metabolism by CYP2D6. [Pg.267]

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. [Pg.462]

Funck-Brentano C, Thomas G, Jacqz-Algrain E, et al. Polymorphism of dextromethorphan metabolism relationships between phenotype, genotype and response to the administration of encainide in humans. J Pharmacol Exp Ther 1992 263 780-786. [Pg.636]

Drugs that are metabolized by the cytochrome P-450 (CYP) isoenzymes CYP2D6, CYP2C9, and CYP2C19 also exhibit genetic polymorphisms. An example of CYP2D6 metabolism is debrisoquine. In about 5-10 /o of Caucasians in North America and Europe and about 1% of Asians, 4-hydroxylation of debrisoquine is reduced, and such individuals are at increased risk for toxicity (orthostatic hypotension). Beta blockers (metoprolol and timolol), antiarrhythmic drugs (encainide and flecainide), tricyclic antidepressants... [Pg.1018]

McAllister CB, Wolfenden HT, Aslanian WS, Woosley RL, Wilkinson GR. Oxidative metabolism of encainide polymorphism, pharmacokinetics and clinical considerations. Xenobiotica 1986 16(5) 483-90. [Pg.1215]

Potentially clinically significant interactions include the tendency for fluvoxamine to increase circulating concentrations of oxidatively metabolized benzodiazepines, clozapine, theophylline, and warfarin. Sertraline and fluoxetine can increase levels of benzodiazepines, clozapine, and warfarin. Paroxetine increases levels of clozapine, theophylline, and warfarin. Fluoxetine also potentiates tricyclic antidepressants and some class 1C antiarrhythmics with a narrow therapeutic index (including encainide, flecainide, and propafenone). Nefazodone potentiates benzodiazepines other than lorazepam and oxazepam. [Pg.160]

Encainide, a class 1C antiarrhythmic agent, is available on a limited basis only to patients with life-threatening ventricular arrhythmias. Encainide slows conduction velocity, inhibits automaticity, and increases the ratio of the effective refractory period to action potential duration. It blocks the sodium channel of Purkinje fibers and the myocardium. Encainide is absorbed well, reaches peak plasma level in 30 to 90 minutes, becomes metabolized to 0-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE), which are active antiarrhythmic agents, and the metabolites are excreted by the kidneys. In renal impairment, the clearance of ODE and MODE is decreased, and hence the dosage should be reduced. Encainide may either worsen or create new arrhythmias, especially in electrolyte-imbalanced patients. Encainide is known to have caused sinus bradycardia, sinus pause, or sinus arrest (see also Eigure 84). [Pg.225]

A a Eh X n Prolongs PR, QRS and QT. PQ/IV. Gl absorption varies widely between patients. 10% of the population metabolizes the drug slowly (4 times slower than remaining 90% of population.) Effects additive with other drugs which affect heart conduction. Cimetidine increases half-life of encainide. ... [Pg.79]

Evidence is lacking for a carrier-mediated oral absorption of these anti-arrhythmic drugs. The general assumption is that the oral absorption of these drugs occurs via a passive process that is nonstereoselective. Except for encainide, propafenone, and verapamil, the oral bioavailability of these drugs is relatively high (>70%). The reported low oral availabilities for racemic encainide (30-88%), propafenone (5-50%), and verapamil (22%) are mostly due to a significant first-pass metabolism rather than incomplete absorption (see the Metabolism section below). [Pg.319]

Hepatic metabolism plays a significant role in the elimination of each of the antiarrhythmics reviewed here. In fact, for propafenone, verapamil, and mexiletine, metabolism accounts for more than 90% of the elimination. Additionally, the biotransformations of mexiletine, propafenone, encainide, and flecainide cosegregate with polymorphic debrisoquine hydroxylation. [Pg.321]

The metabolism of encainide cosegregates with the debrisoquine hydroxylation pathway, which is subject to genetic polymorphism. In humans, encainide is converted to O-demethyl encainide (ODE), which is... [Pg.321]


See other pages where Encainide metabolism is mentioned: [Pg.387]    [Pg.388]    [Pg.216]    [Pg.208]    [Pg.608]    [Pg.1214]    [Pg.1214]    [Pg.6]    [Pg.348]    [Pg.48]    [Pg.322]   
See also in sourсe #XX -- [ Pg.59 ]




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Encainide

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