Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109991
DC Field | Value | Language |
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dc.contributor.author | Vaz-da-Silva, Manuel | - |
dc.contributor.author | Nunes, Teresa | - |
dc.contributor.author | Rocha, José F. | - |
dc.contributor.author | Falcão, Amílcar | - |
dc.contributor.author | Almeida, Luis | - |
dc.contributor.author | Soares-da-Silva, Patrício | - |
dc.date.accessioned | 2023-11-10T12:26:50Z | - |
dc.date.available | 2023-11-10T12:26:50Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 1174-5886 | pt |
dc.identifier.issn | 1179-6901 | pt |
dc.identifier.uri | http://hdl.handle.net/10316/109991 | - |
dc.description.abstract | Background: Etamicastat is a novel, potent, and reversible peripheral dopamineb- hydroxylase inhibitor that has been administered orally at doses up to 600mg once daily for 10 days to male healthy volunteers and appears to be well tolerated. Objective: The aim of this study was to investigate the effect of food on the pharmacokinetics of etamicastat. Material and Methods: A single-center, open-label, randomized, two-way crossover study in 12 healthy male subjects was performed. Subjects were administered a single dose of etamicastat 200mg following either a standard high-fat and high-calorie content meal (test) or 10 hours of fasting (reference). The statistical method for testing the effect of food on the pharmacokinetic parameters of interest was based upon the 90% confidence interval (CI) for the test/reference geometric mean ratio (GMR). The parameters of interest were maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUClast), and AUC from time zero to infinity (AUC¥). Bioequivalence was assumed when the 90% CI fell within the recommended acceptance interval (80, 125). Results: EtamicastatCmax,AUClast, andAUC¥ were 229 ng/mL, 1856 ng h/mL, and 2238 ng h/mL, respectively, following etamicastat in the fasting, and 166 ng/mL, 1737 ng h/mL, and 2119 ng h/mL, respectively, following etamicastat in the fed condition. Etamicastat test/reference GMR was 72.27% (90% CI 64.98, 80.38) for Cmax, 93.59% (90% CI 89.28, 98.11) for AUClast, and 96.47% (90% CI 91.67, 101.53) for AUC¥. Time to Cmax was prolonged by the presence of food (p < 0.001). TheCmax,AUClast, andAUC¥ values of the inactive metabolite BIA 5-961 were 275 ng/mL, 1827 ng h/mL, and 2009 ng h/mL, respectively, in the fasting, and 172 ng/mL, 1450 ng h/mL, and 1677 ng h/mL, respectively, in the fed condition. BIA 5-961 test/reference GMR was 62.42% (90% CI 56.77, 68.63) for Cmax, 79.41% (90% CI 56.77, 68.63) for AUClast, and 83.47% (90% CI 76.62, 90.93) for AUC¥. A total of six mild to moderate unspecific adverse events were reported by four subjects. There was no clinically significant abnormality in laboratory assessments. Conclusion: Etamicastat was well tolerated. The Cmax of etamicastat decreased 28% following oral administration of etamicastat in the presence of food, while AUC remained within the pre-defined acceptance interval. The delay in absorption and decrease in peak exposure of etamicastat is not clinically significant, and therefore etamicastat could be administered without regard to meals. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | BIAL-Portela & Co., SA, S. Mamede do Coronado, Portugal. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | pt |
dc.subject.mesh | Adult | pt |
dc.subject.mesh | Area Under Curve | pt |
dc.subject.mesh | Benzopyrans | pt |
dc.subject.mesh | Biotransformation | pt |
dc.subject.mesh | Cross-Over Studies | pt |
dc.subject.mesh | Dopamine beta-Hydroxylase | pt |
dc.subject.mesh | Enzyme Inhibitors | pt |
dc.subject.mesh | Food Deprivation | pt |
dc.subject.mesh | Food-Drug Interactions | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Imidazoles | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Therapeutic Equivalency | pt |
dc.subject.mesh | Young Adult | pt |
dc.title | Effect of food on the pharmacokinetic profile of etamicastat (BIA 5-453) | pt |
dc.type | article | - |
degois.publication.firstPage | 127 | pt |
degois.publication.lastPage | 136 | pt |
degois.publication.issue | 2 | pt |
degois.publication.title | Drugs in R and D | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.2165/11587080-000000000-00000 | pt |
degois.publication.volume | 11 | pt |
dc.date.embargo | 2011-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.orcid | 0000-0002-3854-6549 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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Effect-of-food-on-the-pharmacokinetic-profile-of-etamicastat-BIA-5453Drugs-in-R-and-D.pdf | 186.87 kB | Adobe PDF | View/Open |
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