Pharmacokinetics and metabolism of encainide

Cardiovascular Drugs and Therapy
P Jaillon

Abstract

The metabolism of encainide occurs in the liver and is polymorphically distributed according to the same genetic factor that determines the 4-hydroxylation of debrisoquine. Over 90% of patients are extensive metabolizers (EM) in whom the oral bioavailability of encainide is only 30% because of extensive first-pass metabolism. In EMs, elimination t1/2 is about 2.5 hours, with a systemic clearance of 1.8 l/min. The plasma concentrations of the major metabolites O-desmethyl-encainide (ODE) and 3-methoxy-O-desmethyl-encainide (3-MODE) are higher than those of encainide and have antiarrhythmic activity. The remaining patients (less than 10%) are poor metabolizers (PM), in whom the oral bioavailability is near 88% with an elimination t1/2 of 8-11 hours and a systemic clearance of 0.2 l/min. Encainide plasma concentrations are 10- to 20-fold higher than in EMs, but considerably less ODE and no 3-MODE is formed by the PMs. The conversion to the N-desmethyl-encainide (NDE) metabolite seems to be similar in both metabolizer groups, and plasma protein binding of encainide of 70-78% is also similar. During long-term treatment, the antiarrhythmic metabolites of encainide accumulate in the plasma, so that the relationships between the effect...Continue Reading

References

Aug 29, 1986·The American Journal of Cardiology·B D QuartA J Wood
Mar 1, 1986·Clinical Pharmacology and Therapeutics·R L WoosleyG R Wilkinson
Aug 29, 1986·The American Journal of Cardiology·D M RodenR L Woosley
Apr 1, 1983·The American Journal of Cardiology·R A WinkleD C Harrison
Apr 1, 1982·Clinical Pharmacology and Therapeutics·R E KatesR A Winkle

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Citations

May 30, 2009·Chemistry & Biodiversity·Bernard Testa, Stefanie D Krämer

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