Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers.

BACKGROUND: Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure. AIM: The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.5 mg of bisoprolol (Bisocard® - the medicinal product) to the original medicinal product (Concor Cor 2.5® - the reference). METHODS: A randomised, open-label, two-period, crossover, single-dose, relative bioavailability study was conducted in fasted healthy Caucasian volunteers. A single 10-mg oral dose (four tablets of 2.5 mg) of the test or reference product was followed by a 14-day wash-out period, after which the subjects received the alternative product. Blood was sampled within a period of 60 h post administration in pre-specified time points. Bisoprolol concentrations were determined by a validated LC-MS/MS method. The products were considered bioequivalent if the 90% confidence interval (CI) of the log-transformed geometric mean ratios (test vs. reference) for AUC(0-t), AUC(0-∞), and Cmax were within 80-125% limits. Adverse events were monitored during the study based on the subject claims and clinical parameters. RESULTS: Twenty-six healthy male and female volunteers (mean age ca. 29 years; body mass index 22.7 kg/m²) were in-cluded in the study, and 24 completed the clinical part. The geometric mean ratios (test/reference) for the log-transformed AUC(0-t), AUC(0-∞), and Cmax were 95.16% (90% CI 92.52-97.87%), 95.08% (90% CI 92.40-97.83%), and 100.00% (90% CI 94.83-105.45%), respectively. There were no significant differences in the pharmacokinetic parameters between the test and reference formulations. No serious adverse events were reported. CONCLUSIONS: The results of this single-dose study in healthy Caucasian volunteers indicate that Bisocard®; 2.5 mg film-coated tablets are bioequivalent to the reference product - Concor Cor 2.5®; 2.5 mg film-coated tablets. Both products had similar safety profile and have been well tolerated.

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.