The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the 
bioavailability and efficacy of levodopa were evaluated in 12 patients with 
Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations 
(wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 
time points before and after the chronic administration of tolcapone using the 
Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved 
at all points of determination. Eight patients with wearing-off phenomenon on 
levodopa showed symptomatic improvement on the combination. The area under the 
curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration 
of tolcapone. The elimination half-life (T1/2) of levodopa was significantly 
prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a 
metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum 
concentration) was also decreased by 80%d after the administration (p = 0.0001) 
of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our 
findings suggest that tolcapone improves the pharmacokinetics of levodopa in 
plasma and motor symptoms of fluctuating PD patients. It is suggested that 
tolcapone may be useful drug adjunct to levodopa in treating patients with PD 
with wearing-off phenomena.