Confirmation of Bioequivalence of Preparation Nebivolol-Darnitsa, Tablets, and Preparation Nebilet®, Tablets13 March 2019
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 AUC0–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 Cmax (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”.