Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 and plasma concentration on encainide, ODE, and 3-MODE are not always obvious. Minimally effective plasma concentrations appear to be approximately 300 ng/ml of encainide, 35 ng/ml of ODE, and 100 ng/ml of 3-MODE. Dose adjustment is necessary in patients with decreased kidney function, but not in patients with cirrhosis, in whom the plasma levels of metabolites appear to be comparable to those in normal subjects.
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PMID:Pharmacokinetics and metabolism of encainide. 212 33

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.
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PMID:Encainide disposition in patients with chronic cirrhosis. 308 68