Linked Life Data

14517707

Source:http://linkedlifedata.com/resource/pubmed/id/14517707

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8-9
pubmed:dateCreated
2003-11-17
pubmed:abstractText
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 (C(max)) of levodopa was found. Mean C(max) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0031-6970
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
603-9
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:14517707-Acetophenones, pubmed-meshheading:14517707-Adolescent, pubmed-meshheading:14517707-Adult, pubmed-meshheading:14517707-Antiparkinson Agents, pubmed-meshheading:14517707-Area Under Curve, pubmed-meshheading:14517707-Benserazide, pubmed-meshheading:14517707-Catechol O-Methyltransferase, pubmed-meshheading:14517707-Cross-Over Studies, pubmed-meshheading:14517707-Dihydroxyphenylalanine, pubmed-meshheading:14517707-Dose-Response Relationship, Drug, pubmed-meshheading:14517707-Double-Blind Method, pubmed-meshheading:14517707-Drug Combinations, pubmed-meshheading:14517707-Drug Interactions, pubmed-meshheading:14517707-Female, pubmed-meshheading:14517707-Half-Life, pubmed-meshheading:14517707-Humans, pubmed-meshheading:14517707-Levodopa, pubmed-meshheading:14517707-Male, pubmed-meshheading:14517707-Middle Aged
pubmed:year
2003
pubmed:articleTitle
Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide.
pubmed:affiliation
Department of Research and Development, BIAL, A Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal.
pubmed:publicationType
Journal Article, Clinical Trial, Randomized Controlled Trial