Authors: Pedro Silveira Manuel VazdaSilva Luis Almeida Joana Maia Amilcar Falcão Ana Loureiro Leonel Torrão Rita Machado Lyndon Wright Patrício SoaresdaSilva
Publish Date: 2003/09/27
Volume: 59, Issue: 8-9, Pages: 603-609
Abstract
BIA 3202 is a novel catecholOmethyltransferase COMT inhibitor being developed for use as a levodopasparing agent in Parkinson’s disease This study investigated the effect of four single oral doses of BIA 3202 50 mg 100 mg 200 mg and 400 mg compared with placebo on plasma concentrations of levodopa and its metabolite 3Omethyllevodopa 3OMD and on inhibition of erythrocyte COMT in healthy subjects receiving 100 mg of levodopa and 25 mg of benserazide Madopar 125 This was a singlecentre doubleblind placebocontrolled randomised crossover study with five singledose treatment periods The washout period between doses was 2 weeks On each treatment period a different dose of BIA 3202 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 3202 significantly increased the area under the concentration–time curve AUC versus placebo ranging from 39 95 confidence intervals 106–169 with 50 mg to 80 95 confidence intervals 142–222 with 400 mg No significant change in mean maximum plasma concentrations Cmax of levodopa was found Mean Cmax and AUC of 3OMD significantly decreased for all doses tested BIA 3202 caused a rapid and reversible inhibition of SCOMT activity ranging from 57 50 mg to 84 400 mg In conclusion the novel COMT inhibitor BIA 3202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3OMD when administered with standard release levodopa/benserazide
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