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Entacapone
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DRUG INFO
Entacapone
Drug Name:
Entacapone
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Indication: For as an adjunct to levodopa / carbidopa to treat patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose "wearing-off".
Pharmacology: Entacapone is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa, catalyzing the metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.
Mechanism Of Action: The mechanism of action of entacapone is believed to be through its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease.
Drug Category: Antiparkinson Agents; Antidyskinetics; Central Nervous System Agents; ATC:N04BX02
Brand Names/Synonyms: Comtan; ENTACAPONE; Entacapona [Inn-Spanish]; Entacapone; Entacapone [Usan:Inn]; Entacaponum [Inn-Latin]
Dosage Forms: TABLET
Absorption: Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
Interactions: Interactions for Entacapone:
In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 to over 1000 uM; an oral 200 mg dose achieves a highest level of approximately 5 uM in people); these enzymes would therefore not be expected to be inhibited in clinical use.
Protein Binding: Entacapone is highly protein bound (98%). In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, salicylic acid, phenylbutazone, and diazepam.
Drugs Metabolized by Catechol-O-methyltransferase (COMT):
Hormone levels: Levodopa is known to depress prolactin secretion and increase growth hormone levels. Treatment with entacapone coadministered with levodopa/dopa decarboxylase inhibitor does not change these effects.
No interaction was noted with the MAO-B inhibitor selegiline in two multiple-dose interaction studies when entacapone was coadministered with a levodopa/dopa decarboxylase inhibitor (n=29). More than 600 Parkinson's disease patients in clinical trials have used selegiline in combination with entacapone and levodopa/dopa decarboxylase inhibitor.
As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g. erythromycin, rifamipicin, ampicillin and chloramphenicol).
No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa/dopa-decarboxylase inhibitor.
Chemical IUPAC Name: 2-cyano-3-(5-dihydroxyamino-3,4-dioxo-1-cyclohexa-1,5-dienyl)-N,N-diethyl-prop-2-enamide
Chemical Formula: C14H15N3O5
Half Life: 0.4-0.7 hour
Drug Type: Approved Drug
# Accession No: APRD00416
CAS Registry Number: 130929-57-6
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