Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research. Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016. Materials and methods : The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters. Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUC ins0-T , and 85.43% - 115.64% for the PD-parameter AUC GIR0_T , which fall within the specified limits of 80% - 125% to establish comparability between drugs. Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®.

Justification. The prevalence of type 2 diabetes is extremely high, and the number of such patients is constantly increasing. In 30-40% of patients, only insulin therapy can achieve compensation for the disease. Therapy with ready-made mixtures is considered as an alternative option in the initiation and intensification of insulin therapy. Rinsulin® mix 30/70 is a domestic biosimilar (bioanalogue) of Humulin® M3, a combination of a 30% solution of human insulin and a 70% suspension of insulin-isofan. The clinical research program for biosimilars of insulin preparations includes pharmacology studies: pharmacokinetics, pharmacodynamics and clinical safety research. Purpose. Evaluation of the biosimilarity of Rinsulin® mix 30/70 (bioanalog) and Humulin® M3 (original) preparations in the conditions of hyperinsulinemic euglycemic clamp in healthy volunteers. Materials and methods. The study was conducted on healthy male volunteers aged 18 to 50 years. Study design is a double-blind, randomized, crossover study of the comparative pharmacokinetics of drugs. The drugs were injected subcutaneously into the anterior abdominal wall at a dose of 0.4 IU / kg once. The duration of blood sampling to determine the pharmacokinetic parameters was 24 hours: the concentration of insulin in the blood was determined by enzyme-linked immunosorbent assay. Based on the level of glycemia, the glucose infusion rate was adjusted, the data of which were used to calculate the pharmacodynamic parameters. Results and discussion. Comparability of the main pharmacokinetic and pharmacodynamic characteristics of the Rinsulin® mix 30/70 and Humulin® M3 preparations in the conditions of hyperinsulinemic euglycemic clamp in healthy volunteers was noted. The confidence interval for the logarithmically transformed ratio of the values of the parameter C ins.max was 87.31-105.26%, and AuC ins.0-12 - 85.23-110.90%, which falls within the limits set by regulatory documents 80-125% to establish comparability between drugs. This confirms the high similarity of the reproduced Rinsulin® Mix 30/70 to the original drug. Of particular clinical significance is the synchronous onset of drug action, the time of onset of the maximum effect and duration of action. Adverse events in the study associated with the introduction of drugs were not recorded. Conclusions. Rinsulin® mix 30/70 and Humulin® M3 are equivalent.

Justification. On average, about 12 % of all global healthcare spending on diabetes. One of the first domestic human insulin preparations was Rinsulin® R, the biosimilar (bioanalog) of Humulin® Regular. The clinical research program for biosimilars of insulin preparations includes pharmacology studies: pharmacokinetics, pharmacodynamics and clinical safety research. Purpose. Evaluation of the biosimilarity of the Rinsulin® R (biosimilar) and Humulin® Regular (original) preparations in the conditions of hyperinsulinemic euglycemic clamp in healthy volunteers. Materials and methods. The study was conducted on healthy male volunteers aged 18 to 50 years. Study design is a double-blind, randomized, cross-sectional study of comparative pharmacokinetics and pharmacodynamics of drugs. The drugs were injected subcutaneously into the anterior abdominal wall at a dose of 0.3 IU / kg once. The duration of blood sampling to determine the pharmacokinetic parameters was 10 hours: the concentration of insulin in the blood was determined by enzyme-linked immunosorbent assay. Based on the level of glycemia, the glucose infusion rate was adjusted, the data of which were used to calculate the pharmacodynamic parameters. Results and discussion. It was found that the studied drugs are characterized by a high degree of similarity of pharmacokinetics and pharmacodynamics. 90 % confidence intervals for the ratios of the geometric mean values of the primary pharmacokinetics AUC ins.0-t and C ins.max fully correspond to the permissible limits of 80-125 % and are, respectively, 88.61-111.52 and 85.411-109,51 %. 95 % confidence intervals for the ratios of the geometric mean values of the primary pharmacodynamics AUC GIR0-t and GIR max fully correspond to the permissible limits of 80-125 % and are, respectively, 93.48-112.29 and 95.75-109.17 %. Of particular clinical significance are the synchronous onset of action of drugs, the time of onset of the maximum effect and duration of action. The frequency of adverse events was comparable in the drug groups. Conclusions. Rinsulin® R and Humulin® Regular are equivalent.

Background: Modern medicine requires use of effective antidiabetic drugs that can imitate the natural profile of insulin in the body of patients with diabetes mellitus. Examples of such preparations include biphasic insulin lispro, which is a mixture of insulin lispro ultra-short action and insulin lispro protamine suspension with prolonged effect. The clinical trials (CT) program for biosimilar insulins contains pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety studies. Aims: To demonstrate Biphasic Insulin Lispro 25, suspension for subcutaneous administration, 100 U/ml (GEROPHARM-Bio, Russia) and Humalog® Mix 25, suspension for subcutaneous administration, 100 U/ml (Lilly France, France) have comparable pharmacokinetic profiles under conditions of hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers. Materials and methods: The study was conducted on 48 healthy men aged between 18 to 50 years. This was a double-blind, randomized, crossover study of comparative pharmacokinetics of drugs. The investigational products (IP) were administered before the clamp in a single dose of 0.4 U/kg subcutaneously in the abdominal wall. Regular blood sampling was performed during the study. The insulin concentrations in the samples were determined using an ELISA method. The results of the determination were used to calculate the PK parameters and construct the concentration-time curves. Adjust glucose infusion rates were based on blood glucose measurements. These data were used to calculate the PD parameters. Results: Our results demonstrated that Biphasic Insulin Lispro 25 and Humalog® Mix 25 have comparable PK and PD profiles under conditions of HEC in healthy volunteers. The confidence intervals for the ratio of the geometric mean for Cins.max and AUCins.0–12 were 87.75–99.90% and 83.76–96.98% respectively, which were well within 80–125% limits for establishing comparability. Conclusions: Biphasic Insulin Lispro 25 and Humalog® Mix 25 are equivalent based on this CT applying the HEC technique in healthy volunteers.