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Acute effects of COMT inhibition on L-DOPA pharmacokinetics in patients treated with carbidopa and selegiline.

The effects of acute catechol-O-methyltransferase (COMT) inhibition on L-DOPA pharmacokinetics were studied in 10 parkinsonian subjects on stable doses of L-DOPA/carbidopa and selegiline. Tolcapone, a reversible COMT inhibitor, was administered in four single ascending doses (50-800 mg) randomly paired with placebo. Serial plasma concentrations of L-DOPA and its metabolites were measured, and patient diaries and clinical ratings of dyskinesia were completed every 30 min for 6 h. Tolcapone increased the area under the curve of the plasma L-DOPA concentration versus time curve and decreased the accumulation of homovanillic acid. COMT inhibition increased "on" time and the duration of dyskinesia without affecting the maximal amplitude of dyskinesia. Tolcapone may be a useful adjunct to L-DOPA/carbidopa.