Autor(es):
Silveira, Pedro 
; Vaz-da-Silva, Manuel ; Almeida, Luís ; Maia, Joana ; Falcão, Amílcar ; Loureiro, Ana ; Torrão, Leonel ; Machado, Rita ; Wright, Lyndon ; Soares-da-Silva, Patrício
Data: 2003
Identificador Persistente: http://hdl.handle.net/10316/2807
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): catechol-O-methyltransferase; COMT inhibition; Pharmacokinetics
Descrição
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.
