ABSTRACT
OBJECTIVE: Evaluation of the bioequivalence of the tested Relonova, tablets, 10 mg and Maxalt, tablets, 10 mg drugs on an empty stomach in healthy volunteers. MATERIAL AND METHODS: The pharmacokinetic analysis population included 40 volunteers, the safety analysis population included 40 volunteers. The average age of randomized volunteers (men - 20, women - 20) was 29.3±8.9 years, height 1.71±0.09 m, body weight 70.86±11.66 kg, mean BMI 24.18±2.81 kg/m2. The method used high performance liquid chromatography with tandem mass spectrometric detection. Statistical analysis of the obtained data was performed based on the assumption of a log-normal distribution of the parameters AUC0-72 and Cmax. RESULTS: The ratio of geometric means for the key pharmacokinetic parameters (AUC0-t, AUC0-inf and Cmax) of rizatriptan is close to 90%, CI is within the acceptable range for bioequivalent drugs (80-125%). The intrasubject variability (CVintra) for rizatriptan was 23.74% (Cmax), 10.94% (AUC0-t). The average profiles of the pharmacokinetic curves of rizatriptan when taking the test and reference drugs have similar shapes. Relonova and reference Maxalt are bioequivalent. CONCLUSION: The results of the study make it possible to recommend Relonova for further clinical study and wide practical application.
Subject(s)
Triazoles , Tryptamines , Adult , Female , Humans , Male , Young Adult , Body Weight , Therapeutic Equivalency , Triazoles/pharmacokinetics , Tryptamines/pharmacokineticsABSTRACT
OBJECTIVE: Evaluation of the efficacy and safety of Levroso Long (fixed dose combination (hereinafter referred to as «FDC¼) diphenhydramine and melatonin, 25 mg + 3 mg and FDC diphenhydramine and melatonin 50 mg + 3 mg, respectively, capsules with modified release, NovaMedica Innotech LLC) in comparison with diphenhydramine medicines 50 mg (Diphenhydramine tablets, DALHIMFARM OJSC, Russia) and 3 mg melatonin (Melaxen tablets, Unipharm Inc., USA) in patients with insomnia. MATERIALS AND METHODS: Material and methods. A multicenter open randomized comparative clinical trial was conducted in parallel groups. The study included 312 patients with an insomnia diagnosis verified in accordance with the DSM-IV criteria (ICD code F51.0-10) and an insomnia severity index (ICI) >8 points. The patients were randomized into 4 groups and took the following medications for 10 days: patients of group 1 - Levroso Long (25 mg diphenhydramine and 3 mg melatonin), group 2 - Levroso Long combination drug (50 mg diphenhydramine and 3 mg melatonin), Group 3 -Diphenhydramine 50 mg, 4th - Melaxen 3 mg. A comparative assessment was performed on the 7th and 10th days of therapy according to the primary endpoint - ICI, and secondary endpoints - the results of the assessment based on the Leeds Sleep Assessment Questionnaire, the Pittsburgh Sleep Quality Questionnaire, the Scale of the overall clinical impression of improvement and the analysis of the profile of adverse events (NA). RESULTS: The FDC of diphenhydramine 25 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg, and FDC diphenhydramine 50 mg + melatonin 3 mg was more effective than diphenhydramine 50 mg or melatonin 3 mg on both primary and secondary endpoints. In a safety assessment, the highest incidence of adverse events (48.7%) in the diphenhydramine 50 mg group was significantly lower in groups 1 (29.5%), 2 (12.8%) and 4 (1.3%). All reported adverse events in the FDC groups were mild or moderate in severity. CONCLUSION: The study showed that Levroso Long in two dosages surpassed monotherapy with 50 mg of Diphenhydramine (50 mg) or Melaxen (3 mg) in patients with insomnia in terms of efficacy parameters. The benefit/risk ratio of the studied drug is favorable compared to monotherapy.
Subject(s)
Melatonin , Sleep Initiation and Maintenance Disorders , Humans , Diphenhydramine/adverse effects , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/chemically induced , Melatonin/adverse effects , Sleep , Treatment OutcomeABSTRACT
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 («CERTARA¼, 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. RESULTS: 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 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. KGaA¼, 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.
