Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa

• Type: Another Publication in an International Scientific Journal
• Date: 2004

Authors

Almeida, L (Author) Other; Vaz Da Silva, M (Author) FMUP; Silveira, P (Author) Other; Falcao, A (Author) Other; Maia, J (Author) Other; Loureiro, A (Author) Other; Torrao, L (Author) Other; Machado, R (Author) Other; Wright, L (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: Clinical Neuropharmacology

Vol. 27

Pages: 17-24

ISSN: 0362-5664

Publisher: Wolters Kluwer Health

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 16 Citations

Other information

Authenticus ID: P-000-CEZ

DOI: 10.1097/00002826-200401000-00007

Abstract (EN): This study investigated the tolerability and the pharma-cokinetic and pharmacodynamic interactions between single oral administration of BIA 3-202 (50 mg, 100 mg, 200 mg, and 400 mg), a novel catechol-O-methyltransferase (COMT) inhibitor, and standard carbidopa/levodopa 25 mg/100 mg (Sinemet 25/100) in healthy adult volunteers. This was a single-center, double-blind, placebo-controlled, randomized, crossover study with 5 single-dose treatment periods with a washout period of 2 weeks between doses. During each treatment period a different dose of BIA 3-202 or placebo was administered concomitantly with Sinemet 25/100. Tolerability was assessed by recording adverse events, vital signs, continuous EKG, and clinical laboratory parameters. Pharmacokinetic parameters of levodopa and 3-O-methyl-levodopa (3-OMD) were determined. The activity of soluble COMT in erythrocytes was also measured. Eighteen subjects (10 men and 8 women) participated in the study. The drug combination was well tolerated, with the adverse events reported being transient and generally mild in severity. Mean levodopa C-max values were attained at 0.8 to 1.8 hours postdose. Thereafter, plasma levodopa levels declined with a mean t 1/2 that increased in a manner that depended on the dose of BIA 3-202. The increase in systemic exposure to levodopa (AUC(0-infinity)) occurred at all doses of BIA 3-202, attaining its maximum at 200 mg BIA 3-202 (95% conficence interval, 1.43-1.73). The mean C-max and AUC(0-infinity) values of 3-OMD decreased dose proportionally in BIA 3-202-treated subjects, with differences being statistically significant for all the doses tested. Maximum COMT inhibition occurred between 0.8 and 2.0 hours postdose, and ranged from 56 (50 mg) to 85% (400 mg). Time to return to baseline COMT activity ranged from 6 (50 mg) to 18 hours (400 mg), following the same dose-dependent tendency. In conclusion, the novel COMT inhibitor BIA 3-202 increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard levodopa/carbidopa.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8