Bioavailability and bioequivalence comparison of brivaracetam 10, 50, 75, and 100 mg tablets and 100 mg intravenous bolus.
OBJECTIVE
To determine the bioequivalence of brivaracetam oral tablet formulations (10, 75, and 100 mg) versus 50 mg oral tablet and to compare the bioavailability of brivaracetam 100 mg intravenous (i.v.) bolus versus 50 and 100 mg tablets, in healthy participants.


METHODS
Phase 1, randomized, open-label, five-period crossover study. Participants received five single doses of brivaracetam: 10, 50 (reference), 75, and 100 mg oral tablets; 100 mg, i.v., bolus injection. Pharmacokinetic parameters (maximum plasma concentration [Cmax ], area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration [AUCt ], area under the plasma concentration-time curve extrapolated to infinity [AUCinf ]) were compared using analysis of variance (ANOVA) following dose normalization and logarithmic transformation. Bioavailability comparisons were based on the 90% confidence intervals (CIs) around the geometric least squares mean ratios (test: reference).


RESULTS
Twenty-five participants were randomized. The 90% CIs around Cmax , AUCt , and AUCinf ratios for brivaracetam 10, 75, and 100 mg tablets versus 50 mg tablet were entirely contained within the bioequivalence limits (0.8000-1.2500). For brivaracetam 100 mg, i.v., bolus, bioequivalence versus 50 and 100 mg tablets was met for AUCt and AUCinf , but Cmax was partly outside the limits (90% CI: 1.1867-1.3863 and 1.1222-1.3136, respectively).


SIGNIFICANCE
Brivaracetam 10, 75, and 100 mg tablets were bioequivalent to the 50 mg tablet. Brivaracetam 100 mg, i.v., bolus had bioavailability similar to that of 50 and 100 mg tablets.
['Stockis|Armel|A|', 'Hartstra|Jan|J|', 'Mollet|Muriel|M|', 'Hadi|Salah|S|']
D000293:Adolescent D000328:Adult D000704:Analysis of Variance D000927:Anticonvulsants D019540:Area Under Curve D001682:Biological Availability D002853:Chromatography, Liquid D018592:Cross-Over Studies D004305:Dose-Response Relationship, Drug D005260:Female D064368:Healthy Volunteers D006801:Humans D008297:Male D008875:Middle Aged D011760:Pyrrolidinones D053719:Tandem Mass Spectrometry D013810:Therapeutic Equivalency D013997:Time Factors D055815:Young Adult
Oral Pharmacokinetics SV2A