Document Detail


Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease.
MedLine Citation:
PMID:  9203084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Yamamoto; M Yokochi; S Kuno; Y Hattori; Y Tsukamoto; H Narabayashi; H Tohgi; Y Mizuno; H Kowa; N Yanagisawa; I Kanazawa
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Journal of neural transmission (Vienna, Austria : 1996)     Volume:  104     ISSN:  0300-9564     ISO Abbreviation:  J Neural Transm     Publication Date:  1997  
Date Detail:
Created Date:  1997-09-03     Completed Date:  1997-09-03     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  9702341     Medline TA:  J Neural Transm     Country:  AUSTRIA    
Other Details:
Languages:  eng     Pagination:  229-36     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aged
Antiparkinson Agents / pharmacokinetics*,  therapeutic use*
Area Under Curve
Benzophenones / therapeutic use*
Catechol O-Methyltransferase / antagonists & inhibitors*
Enzyme Inhibitors / therapeutic use*
Female
Half-Life
Humans
Levodopa / pharmacokinetics*,  therapeutic use*
Male
Middle Aged
Nitrophenols
Parkinson Disease / drug therapy*,  metabolism*,  physiopathology
Tyrosine / analogs & derivatives,  metabolism
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Benzophenones; 0/Enzyme Inhibitors; 0/Nitrophenols; 42HK56048U/Tyrosine; 46627O600J/Levodopa; CIF6334OLY/tolcapone; EC 2.1.1.6/Catechol O-Methyltransferase; V3O7J20DWN/3-methoxytyrosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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