Confirmation of Bioequivalence of Preparation Nebivolol-Darnitsa, Tablets, and Preparation Nebilet®, Tablets

13 March 2019

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Objective. To confirm in comparative randomized two way and two sequence (TR/RT design) cross-over clinical study with participation of healthy volunteers bioequivalence (BE) of preparation Nebivolol-Darnitsa, tablets, 5 mg of nebivolol, manufactured by PrJSC “Pharmaceutical Firm “Darnitsa” (Ukraine), and reference preparation Nebilet^®, tablets, 5 mg of nebivolol, manufactured by Berlin-Chemie AG (Germany).

Researched Subject and Methods. Volunteers of both sexes were administered a single dose, 5 mg of nebivolol, of tested and reference preparations on the empty stomach. Blood samples were taken during 48 hours. Nebivolol assay in plasma samples of volunteers was performed by high-performance liquid chromatography with tandem mass-selective detection.

Results. Data about 40 healthy volunteers were included in analysis of pharmacokinetic parameters. Average values of Сmax for tested preparation Nebivolol-Darnitsa and reference preparation Nebilet^® were 2,282±1,961 ng/ml and 2,228±1,993 ng/ml, respectively, and average AUC_0–t values were 26,954±50,678 ng*h/ml and 27,745±52,206 ng*h /ml, respectively. Limits of 90% confidence intervals for ratios of mean geometric values of C_max (95,37%÷110,30%) and AUC0-t (92,70%÷102,75%) of preparations Nebivolol-Darnitsa and Nebilet^® conform to pre-established acceptability criteria (80,00%÷125,00%). Predictable adverse/side effects (AE/SE) were observed at 2 volunteers, these AE were considered to be not serious.

Conclusion. Bioequivalence of preparation Nebivolol-Darnitsa, tablets, 5 mg, and preparation Nebilet^®, tablets, 5 mg, was confirmed according to the requirements of Instruction ST-N MHU 42-7.2:2018. Both preparations were well tolerated in case of oral administration of single dose on the empty stomach.

This article was prepared due to financial support of PrJSC “Pharmaceutical Firm “Darnitsa”.

Kravchuk Zh.M., Artish BI, Kubesh V., Sotnichenko N.M., Doroshenko A.M. Bioequivalence confirmation of Nebivolol-Darnitsa drug, tablets, Nebilet® drug, tablets: results of a randomized cross-sectional clinical trial involving healthy volunteers. Ukr. Med. Journal, 2019; (129): 31-35.

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