Modifications of plasma and platelet levels of L-DOPA and its direct metabolites during treatment with tolcapone or entacapone in patients with Parkinson's disease.

Abstract

We compared--retrospectively--the effects of a 3-month therapy with catechol- O-methyltransferase (COMT) inhibitors tolcapone (100 mg, t.i.d.) and entacapone (200 mg, t.i.d.), on L-DOPA metabolism in two groups of parkinsonian patients with motor fluctuations. Plasma and platelets concentrations of L-DOPA and its direct metabolites, dopamine and 3- O-methyldopa (3-OMD), were measured before starting treatment, after two weeks and at the end of treatment. Patients treated with tolcapone showed significant increases in plasma and platelet L-DOPA levels and marked reduction of plasma and platelet 3-OMD levels, both at short- and long-term. Entacapone did not modify L-DOPA levels, while inducing a less marked reduction of plasma and platelet 3-OMD concentrations, with respect to tolcapone, at both time points. Both drugs were similarly effective in increasing plasma and platelet levels of dopamine. These results confirm the different profiles of activity of the two drugs, with tolcapone proving more effective on both the intra- and extra-cellular levels of L-DOPA and 3-OMD.