About 20 percent of dofetilide is metabolized in the liver via the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. Drugs that interfere with the activity of the CYP3A4 isoenzyme can increase serum dofetilide levels. If the renal cation exchange system is interfered with (as with the medications listed above), a larger percentage of dofetilide is cleared via the CYP3A4 isoenzyme system. History
After its initial US FDA approval, due to the pro-arrhythmic potential it was only made available to hospitals and prescribers that had received education and undergone specific training in the risks of treatment with dofetilide; however, this restriction was subsequently removed in 2016. See also
Antiarrhythmic agents
Cardiac action potential
Electrocardiogram


== References ==
COMT eliminates biologically active catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered with a decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in the periphery.For the treatment of Parkinsons disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa. Entacapone inhibits COMT in the periphery (but not, or at most marginally, in the brain) and the metabolism of levodopa, thus increasing plasma levels of levodopa and causing more constant dopaminergic stimulation in order to reduce the signs and symptoms presented in the disease. Pharmacokinetics
Absorption
The time to highest blood plasma concentrations is approximately one hour. The substance undergoes extensive first-pass metabolism. Absolute oral bioavailability (F) is 35%. Distribution
The volume of distribution  (Vd) after intravenous injection is approximately 20 liters. 98% of the circulating entacapone is bound to serum albumin, which limits its distribution into tissues. Metabolism and elimination
Entacapone is primarily metabolized to its glucuronide in the liver, and 5% are converted into the Z-isomer. It has a half-life of approximately 0.3–0.7 hours, with only 0.2% being excreted unchanged in the urine. References
External links
"Entacapone". Drug Information Portal. U.S. National Library of Medicine.