Comparative clinical study of the pharmacokinetics and bioequivalence of the combined drug Mioreol and the combined use of mono-drugs containing donepezil and memantine

Abstract

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. 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 AUC0-72 and Cmax. Geometric mean ratio for key pharmacokinetic parameters (AUC0-t, AUC0-####sub/sub#### and Cmax) 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% (Cmax), 6.12% (AUC0-t), and for memantine - 8.13% (Cmax), 6.67% (AUC0-t). The results of the study allow us to recommend Mioreol for further clinical study and wide practical application.