Zeitschrift für Bioäquivalenz und Bioverfügbarkeit

Abstrakt

Bioequivalence of Final Tablet Formulation and Research Tablet Formulation of Eslicarbazepine Acetate in Healthy Volunteers

Ricardo Lima, Teófilo Vasconcelos, Rui Cerdeira, Marc Lefebvre, Eric Sicard, Teresa Nunes, Luis Almeida and Patrício Soares-da- Silva

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.