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.

Validated HPLC method for determination of temozolomide in human plasma.

The aim of the study was to develop a bioanalytical method for the determination of temozolomide (TMZ) in human plasma. Plasma concentration of TMZ was determined on a C18 column after liquid-liquid extraction. Isocratic elution was applied with the mixture of aqueous acetic acid and methanol. Theophylline was used as the internal standard. To prevent chemical degradation of TMZ at physiological pH, plasma samples were acidified to pH < 3. All validation parameters met the acceptance criteria. Calibration curve, prepared using freshly spiked plasma samples, was linear within the range of 0.10-20.00 microg/mL. The method was found to be sufficiently accurate and precise over the studied range of concentrations. TMZ was stable in the acidified plasma samples for at least 50 days at < or = -14 degrees C and < or = -65 degrees C. The method recovery of TMZ from human plasma was consistent and ranged 37.1-41.1%. The developed method is suitable for pharmacokinetic studies in humans after oral administration of TMZ.

Bioequivalence study of 500 mg cefuroxime axetil film-coated tablets in healthy volunteers.

The aim of the study was to investigate the bioavailability of a generic product of 500 mg cefuroxime axetil film-coated tablets (test) as compared to that of a branded product (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 products. A double blinded, randomized, crossover, two-period, single-dose, comparative study was conducted in Caucasian healthy volunteers in fasting conditions. A single oral dose administration of the test or reference product was followed by 7-day wash-out period. The cefuroxime concentration was determined using a validated HPLC-UV method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Tarsime 500 mg manufactured by Tarchominskie Zaklady Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zinnat manufactured by GlaxoSmithKline Export Ltd. (reference product). Both products were well tolerated.