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.

[Measles in Poland in 2001]. / Odra w 2001 roku.

The number of notified measles cases in Poland in 2001 was 133, incidence per 100,000 inhabitants was 0.3. The low incidence has been observed for the last 3 years. Only 73 out of 133 cases were serologically confirmed, 6 other cases were epidemiologically linked to the laboratory confirmed cases. Unvaccinated cases have accounted for almost half of cases. Differences in incidence were noticed across the country and ranged from 0 cases in Opolskie and Zachodniopomorskie voivodeships to 0.7/100,000 in Malopolskie and 1.0/100,000 in Swietokrzyskie voivodeship. The highest incidence was observed in the children one year of age (3.7/100,000) and seven years old (2.3/100,000), however, in general, the age distribution of cases has been shifted toward older ages with 44 cases (33% of all cases) in adults. A proportion of children 13-24 months of age vaccinated with first dose of measles vaccine was 77.1%, and proportion of seven years old children vaccinated with second dose of measles vaccine was 81.7%.

[Hepatitis C in Poland in 2001]. / Wirusowe zapalenie watroby typu C w 2001 roku.

Hepatitis C is a notifiable disease in Poland since 1997. The increasing trend in incidence over the last four years may be explained by continuous improvement of diagnosis and notification. In the year 2001, for the first time since 1997, a number of cases and an incidence of hepatitis C was lower than in preceding years. The total number of 1953 acute and chronic hepatitis C cases has been reported in 2001. Incidence per 100,000 inhabitants was 5.05. The differences in hepatitis C incidence in regard to gender, region and age have been observed. The incidence in urban regions was higher than in rural; 6.49/100,000 and 2.74/100,000, respectively. The incidence among men was higher than in women; 5.87/100,000 and 4.28/100,000, respectively. Coinfection with hepatitis B has been observed in 5.84% of hepatitis C cases.

[Hepatitis A in Poland in 2001]. / Wirusowe zapalenie watroby typu A w 2001 roku.

A total of 738 cases of hepatitis A were reported in 2000, which was 3 times higher as compared to 1999. The incidence rate was estimated to be 1.91 per 100,000. The incidence rate in urban areas was 2 times higher than in rural population. The highest incidence rates were reported among persons 10-14 and 20-24 years old. Patients in these age groups constituted 29.4% of the total number of cases. The above data show that, from 1997 epidemiological situation of hepatitis has been approaching low endemicity pattern.