Diabetes mellitus is the most acute medical and social problem related to the priorities of national health systems. The dramatic and urgent problems of diabetes mellitus are determined by the high prevalence of diabetes, high mortality and early disability of patients. The prevalence of diabetes mellitus in Western countries is 2–5 % of the population, and in developing countries reaches 10–15 %. Inhibitors of dipeptidylpeptidase-4 are one of the classes of drugs for the treatment of patients with diabetes mellitus type II. Now days the analysis of regulatory reports from developed countries show that the number of reports FDA, Health Canada on the risk of serious adverse reactions has increased. Not all detected adverse reactions are listed in the instructions for use among the possible side effects of the group of inhibitors of DPP-4. The article deals with reports of adverse reactions detected during the monitoring of databases of the Russian Federation and regulatory authorities of foreign countries. The safety research of the use of DPP-4 inhibitors is ongoing.

The European Medical Agency (EMA) in 2012 formulated modern legislation defining the procedure for pharmacovigilance — the Good Pharmacovigilance Practices (GVP), which replaced the earlier provisions of the Pharmacovigilance Guidelines for Human Medicines. The signal management position is included in one of the GVP EMA modules and became part of the EAEC GVP Rules. EMA in 2017 published a regulatory guide for detecting a signal in spontaneous reporting databases, which became an Annex to Module IX of the GVP Rules «Signal Management». The approach proposed in the Appendix supplements the classical analysis of disproportionality with other data, based on both statistical and clinical judgments. The article deals with the problem of detecting signals about the safety of medicines. The main parameters that determine the effectiveness of methods for detecting signals on disproportionality and allowing to compare the productivity of different statistical methods with respect to each other are considered. Priority directions are considered when evaluating the signal, and key elements of a qualitative method for detecting signals are drawn up, taking into account the expert opinion.

Around the world, the use of dietary supplements is common and can be purchased without consulting a doctor. It is believed that more than 50 % of adults worldwide use dietary supplements. The article deals with the regulation of the market of biologically active additives worldwide, including the Russian Federation, the safety of use, the development of undesirable reactions. Information was searched on databases on the development of medicinal liver damage associated with the use of biologically active additives containing green tea extract, usninic acid, 1,3-dimethylamylamine, vitamin A, anabolic androgenic steroids, linoleic acid, ephedra, Garcinia Cambogia used for weight loss. The use of anabolic steroids has revealed an increased risk of adverse reactions from the liver, cardiovascular and endocrine systems. The use of dietary supplements containing green tea extract can lead to severe liver damage. Analysis of adverse reactions after the use of dietary supplements under the trade name Herbalife revealed cases of falsification of drugs. The use of drugs containing vitamin a in high doses, ephedra, Garcinia Cambogia led to increased hepatic transaminases, mental disorders, osteoporosis, anorexia.

This article describes basic information about the classification, structure, substrate specificity and expression of organic cation transporters. The pharmacokinetic and pharmacogenetic aspects of transporters are discussed in more detail, as well as their participation in drug-drug interactions. Organic cation transporters are members of the SLC family which include three isoforms: OCT1, OCT2, OCT3. They are similar in structure to other members of this family and have 12 transmembrane domains. OCT1 is expressed predominantly in the liver, OCT2 in the kidneys, and OCT3 is the most common among all transports of this family and is expressed in the liver, placenta, kidneys, skeletal muscles, heart and brain. The regulation of transporter expression is mainly due to the presence of glycosylation and phosphorylation sites in large loops between 1,2 and 6,7 transmembrane domains, respectively. Among the endogenous substrates OCT — catecholamines, neurotransmitters, steroid hormones, etc. Among drugs, substrates of OCT are: metformin, ganciclovir, procainamide, cisplatin, cimetidine, etc. All three OCT genes are located in one cluster with a length of 300,000 bp. on the long arm of the 6th chromosome. For OCT1 the four most studied polymorphisms are known: rs12208357, rs34130495, rs72552763 and rs34059508. For OCT2, the only clinically relevant polymorphism is rs316019. For OCT3 at the moment, there are 4 polymorphisms: A116S, T400I, A439V, and M370I. Drug-drug interactions involving OCT occur when the substrate is inhibitor of the transporter. The effect of cimetidine and platinum drugs on the pharmacokinetics of drugs has been most studied. Organic cation transporters are currently being actively studied. Every year the number of drugs that are substrates of OCT is growing.