Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients
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Abstract
We studied the effect of entacapone, a selective catechol-O-methyltransferase inhibitor, on the bioavailability and clinical effect of levodopa in Parkinson's disease (PD). On day 1 (control day), nine patients received their own levodopa (plus benserazide) medication only; for the next 7 days they received 200 mg of entacapone with each dose of levodopa (tid or qid). We evaluated disability in the morning (8 AM) before drug administration and then at 1-hour intervals until 6 PM on days 1, 2, and 8, using a modified motor part of the Unified Parkinson's Disease Rating Scale. Repeated blood samples were taken before and during the 4 hours after the morning drugs for pharmacokinetic evaluation of entacapone and of levodopa and its metabolites. Added to the levodopa treatment, entacapone decreased clinical disability by about 16% (p < 0.05) from day 1 to day 8. The area under the curve (AUC) of levodopa 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 with entacapone. Entacapone did not change the Tmax and Cmax values of levodopa. After 7 days of treatment with entacapone, the AUC of 3-O-methyldopa had decreased by 44% (p < 0.01) and of homovanillic acid by 26% (p < 0.05) as compared with treatment with levodopa alone. Four patients became slightly more dyskinetic during entacapone treatment than before it. The combination of entacapone and levodopa was well tolerated, judged by the lack of significant changes in hemodynamic and safety variables. We conclude that entacapone may be a helpful adjunct to levodopa in the treatment of PD.
- © 1994 by the American Academy of Neurology
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