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Title: Pharmacokinetic–pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa / benserazide
Authors: Silveira, Pedro 
Vaz-da-Silva, Manuel 
Almeida, Luís 
Maia, Joana 
Falcão, Amílcar 
Loureiro, Ana 
Torrão, Leonel 
Machado, Rita 
Wright, Lyndon 
Soares-da-Silva, Patrício 
Keywords: catechol-O-methyltransferase; COMT inhibition; Pharmacokinetics
Issue Date: 27-Sep-2003
Publisher: Springer-Verlag
Citation: Silveira, Pedro et al. - Pharmacokinetic–pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa / benserazide. Eur J Clin Pharmacol 59 (2003) 603–609
Abstract: BIA 3-202 is a novel catechol-O-methyltransferase (COMT) inhibitor being developed for use as a levodopa-sparing agent in Parkinson_s disease. This study investigated the effect of four single oral doses of BIA 3-202 (50 mg, 100 mg, 200 mg, and 400 mg) compared with placebo on plasma concentrations of levodopa and its metabolite 3-O-methyl-levodopa (3-OMD) and on inhibition of erythrocyte COMT in healthy subjects receiving 100 mg of levodopa and 25 mg of benserazide (Madopar 125). This was a single-centre, double-blind, placebo-controlled, randomised, crossover study with five single-dose treatment periods. The washout period between doses was 2 weeks. On each treatment period, a different dose of BIA 3-202 or placebo was administered concomitantly with Madopar 125. Tolerability was assessed by recording adverse events, vital signs, continuous electrocardiogram and clinical laboratory parameters. In the study, 18 subjects (12 male and 6 female) participated. The drug combination was well tolerated. All doses of BIA 3-202 significantly increased the area under the concentration–time curve (AUC) versus placebo, ranging from 39% (95% confidence intervals, 1.06–1.69) with 50 mg to 80% (95% confidence intervals, 1.42–2.22) with 400 mg. No significant change in mean maximum plasma concentrations (Cmax) of levodopa was found. Mean Cmax and AUC of 3-OMD significantly decreased for all doses tested. BIA 3-202 caused a rapid and reversible inhibition of S-COMT activity, ranging from 57% (50 mg) to 84% (400 mg). In conclusion, the novel COMT inhibitor BIA 3-202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard release levodopa/benserazide.
DOI: 10.1097/00002826-200401000-00007
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais

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