Effect of food on the pharmacokinetic profile of etamicastat (BIA 5-453)

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Vaz Da Silva, M (Author) FMUP; Nunes, T (Author) Other; Rocha, JF (Author) Other; Falcao, A (Author) Other; Almeida, L (Author) Other; soares-da-silva, p (Author) FMUP

Journal

The Journal is awaiting validation by the Administrative Services.

Title: Drugs in R and D

Vol. 11

Pages: 127-136

ISSN: 1174-5886

Indexing

Scopus - 7 Citations

Other information

Authenticus ID: P-007-YTG

DOI: 10.2165/11587080-000000000-00000

Abstract (EN): Background: Etamicastat is a novel, potent, and reversible peripheral dopamineb- ß-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 (C max), area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUC last), and AUC from time zero to infinity (AUC ¿). Bioequivalence was assumed when the 90% CI fell within the recommended acceptance interval (80, 125). Results: Etamicastat C max, AUC last, and AUC ¿ 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 C max, 93.59% (90% CI 89.28, 98.11) for AUC last, and 96.47% (90% CI 91.67, 101.53) for AUC ¿. Time to C max was prolonged by the presence of food (p < 0.001). The C max, AUC last, and AUC ¿ 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 C max, 79.41% (90% CI 56.77, 68.63) for AUC last, 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 C max 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. © 2011 Escudier & Gore, publisher and licensee Adis Data Information BV.

Language: English

Type (Professor's evaluation): Scientific