ABSTRACT
When levodopa is administered with a dopa decarboxylase inhibitor (DDCI), its predominant metabolism is via catechol-O-methyltransferase (COMT). The addition of a COMT inhibitor to levodopa/DDCI therapy extends the levodopa half-life (t½) and increases the concentration area under the curve (AUC). This makes more levodopa available for transport into the brain over a longer duration. COMT inhibitors are indicated for the treatment of Parkinson’s disease patients who are experiencing motor fluctuations on levodopa/DDCI. In clinical trials, COMT inhibitors have been demonstrated to reduce “off” time, increase “on” time, and improve motor function and activities of daily living. Dopaminergic side effects such as an increase in dyskinesia are managed by lowering the levodopa dose. Tolcapone (Tasmar), a very powerful COMT inhibitor, is associated with rare fatal hepatotoxicity and is therefore reserved for patients with an inadequate response to other medications. Entacapone (Comtan) is not associated with hepatotoxicity and liver function test monitoring is not required. A new levodopa/carbidopa/entacapone product (Stalevo) is now available that offers patients the convenience of taking fewer pills per day. There is interest as to whether the use of COMT inhibition from the time levodopa is first introduced can reduce the development of motor fluctuations and dyskinesias.
