Pharmacokinetics of levodopa and effect of catechol-O-methyltransferase inhibitors (COMT)

Inhibition of catechol-O-methyltransferase (COMT) by entacapone and similar compounds, when administered in combination with levodopa plus a dopa-decarboxylase inhibitor, leads to substantial changes in levodopa kinetics. These changes owe to peripheral inhibition of COMT, resulting in plasmatic concentrations of levodopa long enough so that its availability increases as well as its conversion to dopamine in the striatum. This kind of COMT inhibitor does not modify directly the kinetics of levodopa or dopamine in the central nervous system. Peripherally, the effect of COMT inhibition is dosage-dependent and leads to an increase in the systemic availability of administered levodopa. An increase in levodopa half time is the strongest effect in these cases, which results in longer, sustained plasmatic concentrations with no need of an increase in the maximal plasmatic concentrations.