Bioequivalence and pharmacokinetics of two 10-mg bisoprolol formulations as film-coated tablets in healthy white volunteers: a randomized, crossover, open-label, 2-period, single-dose, fasting study.

OBJECTIVE

The aim of the study was to investigate the bioavailability of a generic formulation of 10-mg bisoprolol film coated tablets (test) as compared to that of a branded formulation (reference) at the same strength to determine bioequivalence and to apply for regulatory approval. The secondary objective of the study was to evaluate tolerability of both formulations.

METHODS

A randomized, crossover, open-label, 2-period, single-dose, comparative study was conducted in healthy white volunteers in fasting conditions. A single oral dose administration of the test or reference formulation was followed by a 14-day wash-out period. Blood samples were collected up to 60 hours after dosing. The bisoprolol concentrations in plasma samples were determined using a validated LC-MS/MS method. The formulations were considered bioequivalent if 90% CI of geometric mean ratios (test/reference) for AUC0-t, AUC0-∞ and Cmax were within the range 80.00 - 25.00%. Adverse events were monitored throughout the study based on the clinical parameters and volunteer reports.

RESULTS

Healthy male and female subjects participating in the study had a median (range) age of 23 (20 - 43), weight of 68 kg (52 - 84), height of 172 cm (157 - 184), and BMI of 23.1 kg/m2 (19.3 - 24.9). The 26 consented volunteers have been included and 24 of them completed the clinical part of the study. The geometric mean test/referenceratios (90% CI) for AUC0-t, AUC0-∞ and Cmax were 104.12% (100.52 - 107.85%), 104.05% (100.49 - 107.75%) and 107.91% (103.04 - 112.99%), respectively. All 90% CI were embraced by the 80.00 - 25.00% acceptance interval. No serious adverse events were reported. A total number of 6 non-serious, moderate adverse events were registered, including headache and vomiting in one subject.

CONCLUSIONS

The results of the single-dose study in healthy white volunteers indicated that the film-coated tablets of Bisocard® 10 mg manufactured by ICN Polfa Rzeszów S.A. (test formulation) are bioequivalent to those of Concor 10® manufactured by Merck KGaA (reference formulation). Both formulations were well tolerated.