EFFECT OF ENTACAPONE, A COMT INHIBITOR, ON CLINICAL DISABILITY AND LEVODOPA METABOLISM IN PARKINSONIAN-PATIENTS

We studied the effect of entacapone, a selective catechol-O-methyltran sferase inhibitor, on the bioavailability and clinical effect of levod opa in Parkinson's disease (PD). On day 1 (control day), nine patients received their own levodopa (plus benserazide) medication only; for t he next 7 days they received 200 mg of entacapone with each dose of le vodopa (tid or qid). We evaluated disability in the morning (8 AM) bef ore drug administration and then at 1-hour intervals until 6 PM on day s 1, 2, and 8, using a modified motor part of the Unified Parkinson's Disease Rating Scale. Repeated blood samples were taken before and dur ing the 4 hours after the morning drugs for pharmacokinetic evaluation of entacapone and of levodopa and its metabolites. Added to the levod opa treatment, entacapone decreased clinical disability by about 16% ( p < 0.05) from day 1 to day 8. The area under the curve (AUC) of levod opa increased by 38% (p < 0.01) after administration of a single dose of entacapone and by 40% (p < 0.05) after 7 days of multiple dosing wi th entacapone. Entacapone did not change the T-max and C-max values of levodopa. After 7 days of treatment with entacapone, the AUC of 3-O-m ethyldopa had decreased by 44% (p < 0.01) and of homovanillic acid by 26% (p < 0.05) as compared with treatment with levodopa alone. Four pa tients became slightly more dyskinetic during entacapone treatment tha n before it. The,combination of entacapone and levodopa was well toler ated, judged by the lack of significant changes in hemodynamic and saf ety variables. We conclude that entacapone may be a helpful adjunct to levodopa in the treatment of PD.