Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients

Catechol-O-methyl transferase (COMT) is one of the principal levodopa-metabolizing enzymes, particularly when aromatic amino acid decarboxylase (AAAD) is partially inhibited by carbidopa or benserazide. This paper examines the pharmacology of COMT inhibitors such as tolcapone and entacapone, and considers the effects of these drugs on the pharmacokinetics of levodopa. Both agents extend the elimination half-life and plasma area under the curve of levodopa without affecting the maximal plasma concentration of levodopa (Cmax) or the time until an oral dose of levodopa reaches its peak plasma concentration (Tmax). Clinically, these pharmacokinetic effects permit a reduction in the levodopa dose, an increase in "on" time and a decrease in "off" time in fluctuating PD patients. Motor benefits can also be seen in stable PD patients. COMT inhibitors are thus an alternative to increasing levodopa doses or adding dopamine agonists to reduce "off" time and enhance motor function in fluctuating PD patients. NEUROLOGY 2000;55(Suppl 4):S33-S37.