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Encainide disposition in patients with renal failure
Clinical Pharmacology and Therapeutics
|July 1, 1986
Summary
Patients with renal failure have reduced encainide clearance and increased active metabolite levels, requiring lower encainide doses. This impacts antiarrhythmic drug dosing in kidney impairment.
Area of Science:
- Pharmacology
- Nephrology
- Clinical Therapeutics
Background:
- Encainide is an antiarrhythmic drug metabolized into active compounds, O-desmethylencainide (ODE) and 3-methoxy-ODE (MODE).
- These metabolites contribute significantly to encainide's antiarrhythmic effects and are primarily excreted via urine.
Purpose of the Study:
- To investigate the impact of renal impairment on the pharmacokinetics and disposition of encainide and its active metabolites.
- To compare encainide's effects in patients with renal failure versus healthy individuals.
Main Methods:
- Studied seven extensive metabolizer (EM) patients with renal failure and eight healthy EM volunteers.
- Administered a single dose of encainide and analyzed drug and metabolite levels and ECG parameters.
Main Results:
- Renal failure patients exhibited significantly lower systemic and oral clearances and a shorter elimination half-life of encainide.
- Chronic dosing in renal failure led to substantially higher plasma concentrations of active metabolites ODE (80% increase) and MODE (167% increase).
- Despite higher encainide doses in healthy volunteers, ECG interval prolongations were similar between groups.
Conclusions:
- Patients with renal failure require lower encainide doses due to reduced drug clearance and increased accumulation of active metabolites.
- Renal impairment significantly alters encainide disposition, necessitating dose adjustments for effective and safe antiarrhythmic therapy.