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Encainide disposition in patients with chronic cirrhosis
Author(s) -
Bergstrand Robert H,
Wang Ted,
Roden Dan M,
Avant George R,
Sutton Wade W,
Siddoway Lyle A,
Wolfenden Harold,
Woosley Raymond L,
Wilkinson Grant R,
Wood Alastair J J
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.155
Subject(s) - cirrhosis , bioavailability , pharmacokinetics , pharmacology , drug , medicine , clinical pharmacology , drug metabolism , oral administration , disposition , first pass effect , dosing , active metabolite , psychology , social psychology
The antiarrhythmic agent encainide undergoes extensive first‐pass hepatic metabolism after oral dosing. The active metabolites O ‐desmethylencainide and 3‐methoxy‐ O ‐desmethylencainide are formed in subjects who are extensive metabolizers (EMs), a phenotypic trait that cosegregates with that of debrisoquin. Because of the possibility that drug metabolism is altered by liver dysfunction, the disposition of encainide and its metabolites was studied in six such EMs with cirrhosis and compared with that in eight normal subjects of the same phenotype. Patients with cirrhosis had lower systemic and oral clearances of encainide, resulting in a threefold increase in oral bioavailability. The plasma concentration of encainide was significantly higher among the patients with cirrhosis, whereas the plasma levels of the respective metabolites were comparable with those in normal subjects, resulting in no change in the patient's ECG intervals. Encainide is, therefore, an example of a drug in which cirrhosis causes a three‐ to fourfold increase in parent drug concentrations. However, because no change occurs in the levels of the pharmacologically active metabolites, dosage adjustment is probably not required in patients with cirrhosis. Clinical Pharmacology and Therapeutics (1986) 40, 148–154; doi: 10.1038/clpt.1986.155