Research Article
Ricardo Lima, Teófilo
Abstract
Purpose: To investigate the bioequivalence of the final tablet formulation of eslicarbazepine acetate (ESL) and the tablet formulation used in pivotal clinical stu dies. Methods: Single centre (Algorithme Pharma, Quebec, Canada) study consisting of three single-dose, rand om- ized, two-way crossover sub-studies in healthy subj ects. In each sub-study (n=20), the bioavailability of BI A 2- 005 (ESL active metabolite) following a given ESL t ablet strength (400 mg, 600 mg or 800 mg) of the final fo rmula- tion (Test) was compared with the corresponding tab let strength of the research formulation (Reference), u nder fasting conditions. The statistical method for test ing bioequivalence was based upon the 90% confidence in ter- val (90%CI) for the Test/Reference geometric mean r atio (GMR) for C max , AUC 0-t and AUC 0- ∞ . Bioequivalence was to be assumed when the 90%CI fell within the recom- mended acceptance interval 80.00%; 125.00%. Results: The Test/Reference GMR and 90%CI for BIA 2-005 were as follows: 400 mg tablets – 105.37% (99 .57%; 111.52%), 102.83 (99.19%; 106.61%) and 102.83% (99.13%; 106.66%) for C max , AUC 0-t and AUC 0- ∞ , respec- tively; 600 mg tablets – 102.65% (97.27%; 108.33%), 102.40% (99.00%; 105.93%) and 102.38% (98.97%; 105.90%) for C max , AUC 0-t and AUC 0- ∞ , respectively; 800 mg tablets – 104.16% (95.44%; 113.67%), 100.34% (97.85%; 102.90%) and 99.88% (97.65%; 102.16%) for C max , AUC 0-t and AUC 0- ∞ , respectively. Conclusion: The 90%CI of all pharmacokinetic param- eters of interest (C max , AUC 0-t , and AUC 0- ∞ ) fell within the acceptance range of 80.00%; 125.00%. Therefore, bioequivalence of the final tablet formulation and the tab- let formulation used in the pivotal clinical trials of ESL has been demonstrated.