Confirmation of bioequivalence of Nebivolol-Darnitsa, tablets, and Nebilet®, tablets: results of a randomized crossover clinical trial in healthy volunteers | Ukrainian Medical Journal

Artysh B.,Doroshenko A.,Sontikhenko N.M.,Kubeš V.

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Confirmation of bioequivalence of Nebivolol-Darnitsa, tablets, and Nebilet®, tablets: results of a randomized crossover clinical trial in healthy volunteers

Confirmation of bioequivalence of Nebivolol-Darnitsa, tablets, and Nebilet®, tablets: results of a randomized crossover clinical trial in healthy volunteers

March 7, 2019

1043

Cardiology, Rheumatology

Therapy, General practice

Specialities :

Cardiology, Rheumatology

Therapy, General practice

Resume

The aim is to prove the bioequivalence of the test product Nebivolol-Darnitsa 5 mg tablets of nebivolol, manufactured by PJSC «Pharmaceutical Firm «Darnitsa» (Ukraine), and the reference product Nebilet® 5 mg tablets of nebivolol, manufactured by Berlin-Chemi AG (Germany), in a comparative randomized two-period two-sequence (TR/RT) crossover clinical trial in healthy volunteers. Materials and methods. Volunteers of both sexes took in the fasting condition a single 5 mg nebivolol dose of the test and reference drugs. Blood samples were taken within 48 hours. Quantitative determination of nebivolol in blood plasma of the volunteers was performed using high performance liquid chromatography with tandem mass selective detection. Results. Data from 40 healthy volunteers were included in the analysis of pharmacokinetics. For Nebivolol-Darnitsa and Nebilet®, mean nebivolol C_max values were 2.282±1.961 and 2.228±1.993 ng/ml, respectively, and corresponding mean AUC0_–t values were 26.954±50.678 and 27.745±52.206 ng‧h/mL, respectively. The ranges of 90% confidence intervals of geometric mean ratio for C_max (95.37–110.30%) and AUC0_–t (92.70–102.75%) for Nebololol-Darnitsa and Nebilet® meet prespecified acceptance criteria (80.00–125.00%). Suspected adverse reactions/events were observed in 2 volunteers and were considered to be non-serious. Conclusions. The bioequivalence of Nebivolol-Darnitsa, 5 mg tablets, and the reference product Nebilet®, 5 mg tablets, was proven in accirdance with the guidelines on bioequivalence testing (СТ-Н МОЗУ 42-7.2:2018). Both drugs were well-tolerated following a single dose oral administration in the fasting state.

Published: 07.03.2019

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