OBJECTIVE

The study of bioequivalence and safety of the fixed combination of the drug Mioreol (Donepezil + Memantine, 10 mg + 20 mg) in relation to the combined use of Yasnal 10 mg and Akatinol Memantin 20 mg.

MATERIAL AND METHODS

The safety analysis study included 36 male (n=8) and female (n=10) subjects, sexes (age 26.3±7.1 years, body mass index (BMI) 23.0±2.8 kg/m²). In the study for the analysis of pharmacokinetics — 31 male (n=8) and female (n=10) persons (age 26.5±7.9 years, BMI 23.5±3.1 kg/m²). The method used high performance liquid chromatography with tandem mass spectrometric detection. Pharmacokinetic analysis was carried out using Phoenix WinNonlin software («CERTARA», Pharsight, USA) v. 8.2. Statistical analysis of the obtained data was performed based on the assumption of a lognormal distribution of parameters AUC_0—72 and C_max.

RESULTS

Geometric mean ratio for key pharmacokinetic parameters (AUC_0—t, AUC_0—####sub/sub#### and C_max) donepezil and memantine are close to 100% and 90%, measuring ranges are within acceptable limits for bioequivalent drugs range (80—125%) for both active ingredients. Within-subject variability (CVintra) for donepezil was 9.34% (C_max), 6.12% (AUC_0—t), and for memantine — 8.13% (C_max), 6.67% (AUC_0—t).

The average profiles of the pharmacokinetic curves of donepezil and memantine when taking the test drug and the combination of comparator drugs have similar forms. Fixed combination Mioreol (Donepezil + Memantine, drug, 10 mg + 20 mg) and Yasnal preparations 10 mg (Krka JSC, d.d., Novo Mesto) and Akatinol Memantine 20 mg («Merz Pharma GmbH and Co. KGaA», Germany) when taken together are bioequivalent.

CONCLUSION

The results of the study allow us to recommend Mioreol for further clinical study and wide practical application.