This paper summarises scientific literature on pharmacotherapy of epilepsy in pregnant women from the perspective of clinical pharmacology. It analyses general principles of antiepileptic therapy in pregnant women. It was demonstrated that the optimal conditions for treating epilepsy during pregnancy involve the use of the minimum dose of an anticonvulsant. The article describes specific pharmacokinetic parameters of antiepileptic drugs (valproic acid, carbamazepine, lamotrigine, phenytoin, phenobarbital) that require adjustment of the dose regimen based on therapeutic drug monitoring. It was demonstrated that carriership of «slow» allelic variants of CYP2C9 is associated with a slowdown in hepatic biotransformation of valproic acid, carbamazepine, topiramate, phenytoin, oxcarbazepine, diazepam, phenobarbital, and primidone, and, consequently, with increased drug concentrations in blood plasma and an increased risk of adverse reactions. Taking into account polymorphism of genes encoding metabolic isoenzymes of traditional antiepileptic drugs, it is recommended for pregnant women and women planning a pregnancy to undergo genotyping. It was demonstrated that polymorphism of the ABCB1 gene and genes of other transport proteins can modify the effect of antiepileptic drugs on the foetus, thus increasing the teratogenic risk.

The article presents general data on the chemical composition and properties of snake venoms, as well as the history of their use in medical practice. It considers the differences characteristic of the venom of snakes belonging to different systematic groups. It demonstrates that venoms remain a valuable source of new medicines. The article compares existing methods of venom analysis (immunological, chromatographic, electrophoretic, mass spectrometric). Particular attention is paid to specific metho-dological aspects of identification testing depending on the object and purpose of the analysis. The article also compares different modifications of the precipitation reaction. It highlights the advantages and disadvantages of existing methods. The affordability and simplicity of immunological methods accounts for their wide use in the analysis of poisons in biological media which helps to determine the cause of poisoning. While greater informativeness of instrumental methods makes them a perfect toll for detailed examination of poison composition during poisons research and comparison. The authors of the article performed  a retrospective analysis of data obtained in identification testing of snake venoms during the period from 2006 to 2017. It has been established that manufacturer specifications for individual medicinal products in some cases do not contain instructions on the use of a specific type of precipitation reaction or the description of test procedures. It was concluded that some modifications should be made to the existing method, the choice of conditions for sample preparation should be considered, or alternative methods for identification of snake venoms in medicinal products should be developed.

The use of medicinal plants for therapeutic purposes (herbal medicine) is still popular nowadays. The aim of the present paper was to analyse registration dossiers for herbal medicines submitted for expert evaluation in accordance with the current national legal requirements for dossier compilation and methodological approaches to the examination of the benefit-risk ratio of herbal medicinal products. The article describes specific features of the preclinical and clinical sections of the common technical document for herbal medicinal products. The article also considers current national requirements for safety and efficacy evaluation of herbal medicinal products. It analyses specific aspects of preclinical (toxicological, pharmacokinetic and pharmacological) and clinical trials of medicines. Based on the results of the analysis the authors elucidate the main mistakes in the preparation of the necessary documents for registration dossiers for herbal medicinal products, namely: lack of complete information on the preclinical toxicological study of the product; inconsistencies in the product composition as specified in different documents; lack of statistical analysis of the results of studies; errors in draft patient information leaflets for herbal medicinal products. The materials presented in the article are high on the agenda and will help applicants properly compile registration dossiers for herbal medicinal products.

The article analyses regulatory documents and requirements for statistical principles of planning and evaluation of results of bioequivalence studies. It describes current statistical approaches to bioequivalence evaluation and relevant recommendations for the planning of studies of conventional medicinal products, medicinal products with a narrow therapeutic range, and analogues of endogenous compounds. The article analyses such statistical approaches as average Bioequivalence (ABE), Average Bioequivalence with Expanding Limits (ABEL), Reference-Scaled Average Bioequivalence (RSABE). It describes specific aspects of statistical analysis of insufficiently studied medicinal products. The article also describes acceptable algorithms of planning and performing two-stage bioequivalence study designs, since such studies call for multiple testing of the bioequivalence hypothesis which leads to an increased probability of type i error (consumer risk). The article offers recommendations for the choice of statistical approaches and describes some aspects of statistical analysis methods depending on the design of the study and the type of generic medicines.

The article dwells upon the development and implementation of a computerised information system for automation of expert work related to evaluation of medicines interchangeability parameters. The article analyses the results of application of a process-oriented approach to the development and implementation of an interchangeability evaluation algorithm in an expert institution. The article suggests step-by-step solutions for the development of an information system that will make it possible to automate standard operating procedures and help substantiate expert conclusions. The article provides basic legal and regulatory as well as scientific and technological information necessary for the creation of an information systems project for the development of a single intranet environment of an expert institution ensuring the automation of all key technological processes that rest upon single systematic approaches and principles. It was demonstrated that introduction of the designed information system in the institution ensures efficient implementation of standard operating procedures when assessing medicines interchangeability.

This article describes the results of Laboratory Information Management System implementation in an expert institution dealing with medicines evaluation. The purpose of the study was to evaluate the feasibility of providing digital support to the laboratories of the Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation and to assess the functionality of the information system in terms of coverage of functional capabilities of various classes of laboratory software. The implementation of laboratory automation systems is required by the current regulations and is in line with international approaches to organisation of the quality management. The information system implementation made it possible to computerize management of drug samples, distribution of assignments among responsible employees, storage and management of documents, and reporting of test results. It created opportunities for direct integration with laboratory equipment allowing for creation of analytical protocols without manual data transfer. The implemented solution meets all requirements and standards for the functional capabilities of laboratory information systems. A similar system could be used in chemical, pharmacological, medical and biochemical laboratories, its implementation will make it possible to meet both national and international standards. These innovations are part of the concept of CALS/PLM technologies integration into institutions management programmes.

The article describes theoretical foundations and successful experimental testing of a modified method of intravitreal injection (IVI) in the rabbit eye performed in the laboratory. The method needed modification because preoperative preparation described in available guidelines on IVI requires the use of medicines that are not suitable for use in vivariums in the Russian Federation. The IVI procedure for rabbits was modified by using an anesthetic regime reproducible in Russia and available eye preparations. The anesthetics used were Zoletil 50® («Virbac», France) At a dose of 1.1 mg/kg and Rometar («Bioveta, a.s.», Czech Republic) At a single intravenous dose of 5.6 mg/kg. additional analgesia was achieved by a single intramuscular injection of Ketonal® («Lek d.d.», Slovenia) At a dose of 5 mg/kg. The local anesthetic used was Inokain® eye drops («Promed Exports Pvt. Ltd.», India), the antiseptic used was Betadine® (JSC «EGIS Pharmaceutical plant», Hungary) diluted with water in the proportion of 1:10. The results of clinical examination of animals following IVI performed by lab researchers during unassisted skill training were analysed, and the results of assessment of adverse reactions associated with IVI were expressed as scores and reflected in primary records. The suggested method demonstrated good reproducibility and, therefore, may be recommended for use in preclinical studies of ophthalmic drug products in Russia.

At present all new medicinal products and cosmetics that absorb medium-wavelength UVB, long-wavelength UVA, or visible light in the range 290–700 nm need to be tested for potential phototoxicity. phototoxicity is evaluated by both in vitro and in vivo methods. There are guidelines for in vitro phototoxicity evaluation, however, there are no formally validated protocols for in vivo phototoxicity evaluation. The purpose of this study was to test an economically viable and informative method for in vivo evaluation of tetracycline and ketorolac phototoxicity using outbred rats. Two medicinal products potentially capable of causing clinically established phototoxic reactions were used in this study: tetracycline (tablets, 200 mg/kg and 300 mg/kg) and ketorolac (gel, 13.4 mg/kg, 26.8 mg/kg and 40.3 mg/kg). The medicines were administered in both single and multiple doses. Ultraviolet irradiator OUFK-03 (OOO «Solnyshko», Russia) was used as a light source. The UV exposure (5 J/cm2 and 15 J/cm²) was performed once 1 h after medicine administration. The skin reaction was evaluated 30 minutes and 24 hours after irradiation and then daily for 2 weeks. As a result, the following optimal parameters were determined for in vivo evaluation of phototoxic reactions caused by the medicines: radiation intensity — 15 J/cm² for single systemic administration and 5 J/cm² for single topical (dermal) administration; recommended period of skin reaction evaluation for outbred rats is not less than 7 days.

The article describes standard methodological approaches to the determination of subvisible particles by electrical sensing zone method (the Coulter principle). The standard procedure of lyophilisate and powder preparation includes their dilution with Isoton® II Diluent (Beckman Coulter, USA) — 0.9 % sodium chloride solution containing a preservative agent (hereinafter — Isoton) under conditions free from particulate matter. The article provides a brief description of the Coulter principle which was included into the General monograph «Subvisible particulate matter in parenteral preparations» of the State Pharmacopoeia of the Russian Federation, 13th edition. It was demonstrated that most solutions for injection and infusion do not need special preparation before testing, whereas 13 % of such preparations need the addition of the diluent Isoton to increase their electrical conductivity for determination of subvisible particulate matter. The article presents the results of experimental studies that were aimed at modification of the standard sample preparation procedure for different medicinal products for the purpose of their evaluation in terms of subvisible particulate matter. A number of lyophilisates, powders, suspensions, and oily solutions can not be diluted with Isoton because of precipitate formation, so recommendations are offered for these types of products regarding the choice of alternative diluents (water, 4 % sodium chloride solution, ammonium thiocyanate solution in isopropanol, acetone, etc.) for obtaining electrically conductive solutions. Alternatively, it may be recommended to change the dilution mode (increase the time of dilution and/or diluent volume). Thus, the article provides rationale for using the Coulter principle for determination of subvisible particulate matter in various pharmaceutical forms.

The article looks into the main problems of determination of iodine trace amounts in multivitamins by inductively coupled plasma-atomic emission spectrometry (ICP-AES), i.e. spectral overlaps attributable to macro-components, and the background effect of organic compounds. The article suggests potential ways of solving these problems. It was shown that there was a minimal overlap of iodine spectral lines by emission lines of multivitamins macro-components at the non-priority wavelength of 182.276 nm. The iodine detection limit (LOD) and limit of quantification (LOQ) were experimentally determined for ICP-AES at different wavelengths. It was demonstrated that LOD and LOQ of iodide ion were much higher in solutions containing a complex organic and multi-element matrix then in water solutions, which calls for the use of spiking in iodine assays. A comparative analysis was performed in which the content of iodine was determined in the multivitamin product Multi-tabs Junior by ICP-AES and by the reference method of inductively coupled plasma-mass spectrometry (ICP-MS). It was demonstrated that the increase in plasma power to 1500 W, the use of spiking which minimizes the background interference of organic compounds, and the use of non-priority wavelength (182.276 nm) make it possible to obtain results of iodine determination in mulitivitamins by ICP-AES which are comparable to the results obtained by the reference method.