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Drugs R D. 2011;11(2):127-36. doi: 10.2165/11587080-000000000-00000.

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

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Department of Research and Development, BIAL-Portela Co., SA, S. Mamede do Coronado, Portugal.



Etamicastat is a novel, potent, and reversible peripheral dopamine-β-hydroxylase inhibitor that has been administered orally at doses up to 600 mg once daily for 10 days to male healthy volunteers and appears to be well tolerated.


The aim of this study was to investigate the effect of food on the pharmacokinetics of etamicastat.


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 200 mg 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).


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.


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.


EudraCT No. 2007-006530-33.

[Indexed for MEDLINE]
Free PMC Article

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