Research findings demonstrate the possibility of replacing the vaccines, when used in accordance with the recommended dosage and administration schedule specified by the manufacturer. Control and regulatory authorities in many countries publish recommendations on how to proceed in case of the need to replace a vaccine with a similar one. However, in Russia there are no special normative documents regulating interchangeability of vaccines. It is necessary to define the concept of «interchangeability» of a vaccine as «changeability» and extend it to the possibility of continuing immunization course in a specific patient using a drug from a different manufacturer and the possibility of using vaccines with similar therapeutic indications produced by various manufacturers.

The article presents a review of modern regulatory and legal framework and draft regulatory documents on circulation of interchangeable drugs with regard to standard instructions for medical use. The analysis included more than 70 documents. There are two slightly different notions in this field: a generic drug and an interchangeable drug. A generic drug is not necessarily an interchangeable drug. The interchangeability of a drug is determined during pre-marketing evaluation. Some differences concerning normative requirements to the content of standard instructions for interchangeable drugs have been observed when comparing the regulatory framework of Russia, CIS countries and the EU. It is necessary to look not only at bioequivalence as an equivalent of interchangeability, but also take into account characteristics of excipients, and therapeutic equivalence based on preclinical and clinical trial results. The analysis of differences in regulatory documents can form the basis for further harmonization of requirements to instructions for medical use of interchangeable drugs.

The article investigates the possibility of using thin-layer chromatography and spectrodensitometer analysis of TLC-chromatograms to determine impurities in ciprofloxacin tablets. HPTLC silica gel 60F₂₅₄ chromatographic plates and the mobile phase dichloromethane:methanol:ammonia:acetonitrile (30:40:20:10) were used to obtain chromatograms that enabled quantitative determination of ciprofloxacin ethylenediamine analogue in the tablet dosage form. The results of testing were consistent with the data obtained by a validated method. The proposed method makes it possible to determine an identified impurity if the data obtained from tests do not comply with the specification.

We have conducted an analysis of literature data on results of clinical trials suggesting that bioactive substances in some herbal medicinal preparations influence the efficacy and safety of medicines comprising various pharmacological classes if used concomitantly. Types of interactions between bioactive substances as a part of herbal medicines and chemically synthesized drugs have been discussed. It has been shown that in the case of concomitant use herbal medicinal products influence the pharmacodynamics of chemically synthesized drugs. This can either result in better safety and efficacy, or in adverse reactions. It is proved to be necessary to unify safety sections of patient information leaflets for herbal medicinal products approved in Russia for human use.

Preeclampsia is a frequent and dangerous disease in pregnancy which has shown no decrease in incidence. The article describes preeclampsia pathogenesis as reported in recent studies. A promising trend in the development of new medicines aimed at prevention and treatment of preeclampsia is the activation of biological processes of cytoprotection which arise during ischemic preconditioning. The article cites experimental and clinical data that help to justify the good potential of this area of research.

One of the common issues of modern medicine is the risk of adverse drug effects when administering certain medicines. The causes of these effects may be various, but they mostly occur because of increased or decreased activity of xenobiotic-metabolizing enzymes, based on cytochrome P450 isoenzyme system (also known as CYP). For the date there is a number of different ways to determine the activity of the mentioned system in specific patient. The authors have studied the basic methods of determining the activity of drug-metabolizing enzymes and the approaches to their introduction into clinical practice, as well as the prospects of using them for the purpose of personalization of pharmacy and pharmacotherapy rationalization.

The blood plasma IgG autoantibodies to human protein S-100, to NMDA-receptors and to dopamine receptor type 2 were determined in 13 epilepsy patients with secondary generalized seizures, 16 - in Parkinson patients, 33 - in schizophrenia patients at the age of 18-78. All the enrollees were male. The level of antibodies to S-100 in patients with Parkinson’s was close to normal, it was increased in epilepsy patients and in 59 % of schizophrenia patients. Herewith, in 41 % of schizophrenia patients the levels of autoantibodies to protein S-100 were within normal range. The level of autoantibodies to NMDA-receptors was moderately increased in patients with Parkinson’s and noticeably increased in patients with epilepsy. 45 % of patients with schizophrenia showed a significant increase in NMDA receptor autoantibodies, the others - had normal levels of antibodies. The level of autoantibodies to dopamine receptors in patients with Parkinson’s was normal, and in patients with epilepsy it was significantly increased. In 21 % of patients with schizophrenia the level of autoantibodies to dopamine receptors was normal and in 79 % of patients had significantly increased level of autoantibodies. In patients with schizophrenia high levels of antibodies to dopamine receptors overlapped with high levels of autoantibodies to S-100.

The article investigates the possibility of streamlining the methodology of clinical studies of next-in-class drugs by implementing an adaptive design. Next-in-class drugs are original drugs with known biological targets, similar in structure and mode of action to already existing well-established innovative products. The results of phase II-III clinical trials are illustrated by three investigational products of different pharmacological classes, including a DPP-4 inhibitor (Diabetes mellitus type 2), factor Xa inhibitor (VTE prevention in orthopedic surgery), and NNRTI (HIV). A two-stage «seamless» adaptive design was developed for the clinical trials. In all the three studies the non-inferiority hypothesis was tested versus the standards of care. The adaptive design in DPP-4 inhibitor study made it possible to assess the efficacy and safety of two consecutive treatment regiments (mono- and combination therapy). The optimal doses for factor Xa inhibitor and NNRTI were selected at Stage 1, and their efficacy and safety were tested at Stage 2. The non-inferiority vs. standards of care was successfully demonstrated for all investigational products. The introduction of the adaptive design resulted in the optimization of the clinical programs of the next-in-class drugs.

The influence of vitamins with antioxidant properties (vitamins A, E, C), B vitamins (B1, B2, B6) and vitamin-like substances (coenzyme Q10, taurine and L-carnitine) on the enzymes of the first phase of xenobiotic metabolism - cytochromes P450 3A4 and P450 2C9 has been studied. The experiments with informed volunteers have shown that B vitamins can shorten the duration of nonsteroidal anti-inflammatory drug diclofenac therapy and reduce the daily need for it. The positive effect of B vitamins in reducing the pain syndrome, shortening the duration of therapy and reducing the need for daily intake of diclofenac. Pharmacodynamic and pharmacokinetic data have been confirmed by electrochemical tests of electrocatalytic activity of cytochrome P450 3A4 (CYP3A4). Electrochemical approach to the study of catalytic activity of cytochrome P450 and the impact of vitamins and natural compounds on electrocatalysis is an accurate and effective touch-sensitive method allowing to use low concentrations of protein at an electrode (10-15 mol/electrode), to conduct the analysis without using protein pairs (cytochrome B5, NADPH-dependent reductase) and to identify the interaction of drugs in preclinical studies. When comparing the influence of B vitamins (B1, B2, B6) in the same concentration (300 μM) according to the electrochemical analysis, riboflavin (vitamin B2) is most effectively inhibits the interaction of diclofenac with cytochrome P450 3A4. Vitamin-like substance taurine with antioxidant properties and antioxidant vitamins stimulated electrochemical reduction of cytochromes P450 3A4 and P450 2C9. The obtained data confirm that it is possible that the influence of vitamins on cytochromes P450 3A4 (CYP3A4) и P450 2C9 (CYP2C9) allows to regulate pharmacokinetic parameters and the pharmacodynamic effect intensity.

The article describes the system of electronic document management related to the certification of medicinal immunobiological products (MIBP) in the Scientific Centre for Expert Evaluation of Medicinal Products», as well as historical aspects of its development. It also provides a brief description of CALS - the resources introduced into the expert institution’s activities, which are necessary for maintaining the life cycle of medicinal products. It specifies the main tasks that could be solved with the help of the IS «Document flow related to certification of MIBPs». The article enumerates the main development stages of the information system and its functional capabilities. It contains a review of certain modules of the IS «Document flow related to certification of MIBPs», implemented to meet modern standards of information security. It also summarizes the findings of the development of the IS «Document flow related to certification of MIBPs». The prospects of using the IS «Document flow related to certification of MIBPs» in the expert and scientific activities of the institution are also provided.

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.

The article discusses therapeutic drug monitoring (TDM) data for clozapine obtained in patients with various forms of schizophrenia undergoing treatment in hospital. Clozapine and its metabolite norclozapine concentrations and their response to the administered drug doses have been studied. Clozapine and norclozapine assay in human blood has been performed by high performance liquid chromatography with mass spectrometric detection. Monitoring and subsequent data analysis has been supported with necessary clinical information in the form of special requests - TDM cards. The obtained data on concentration levels have been arranged as follows: 38.64 % within therapeutic range, 38.64 % within subtherapeutic range (<350 ng/ml) and 22.73 % within arbitrary toxic range (600 ng/ml) when administering 25 to 30 mg of clozapine daily. Average concentrations of clozapine and norclozapine were higher in non-smokers compared to smokers.