Фармакокинетика и Фармакодинамика (Sep 2019)
Biosimilar of biphasic human insulin: results of a double-blind, randomized, comparative, cross-sectional clinical study of pharmacokinetics
Abstract
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 Cins.max was 87.31-105.26%, and AuCins.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.
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