Vol 49, No 11 (2016)

The pharmacokinetics of ubidecarenone (CoQ10) in rat plasma and the kinetics of its organ levels were studied for the first time for 8-16 d after a single i.v. injection at a dose of 30 mg/kg. The pharmacokinetics followed a classical two-compartment curve. The main pharmacokinetic parameters for plasma (C₀, AUC_0→∞, K_α, K_el, t_1/2α, t_1/2el, Cl_T, V_d) and several organs (C_max, T_max, AUC_0→t, f_tiss) were calculated. The results proved that CoQ₁₀ injected i.v. rapidly attained and maintained for a long time high levels in plasma, myocardium, brain, liver, and kidneys. This was potentially important for treating acute ischemic states.

Data on the biological activities of compounds containing m-dinitroaromatic (m-DAr) moieties were presented and led to the conclusion that including this moiety in the structures of new biologically active compounds was promising. It was established that one nitro group in m-DAr could be replaced by trifluoromethyl without losing the biological activity of the obtained analogs.

Condensation of 1-substituted 2-aminobenzimidazoles with aromatic aldehydes produced the corresponding azomethines, reduction of which by sodium borohydride afforded 1-substituted 2-benzylaminobenzimidazoles. The Microcosm information technology (IT) tool was used to assess in silico the potential for antiarrhythmic, antiaggregant, antioxidant, hemorheologic, and antiglycating activity in this series of compounds. Pharmacological screening identified which of the synthesized compounds were active. It was shown that the computer predictions correlated with the experimental data.

A synthetic method for 2,4-dimethoxyphenylbiguanide, which was selected using the Prediction of Activity Spectra of Substances (PASS) computer program, was developed. The influence of this novel biguanidine derivative on the content of reduced glutathione and the activities of glutathione peroxidase, glutathione reductase, and glutathione transferase in the heart and blood serum of rats with experimental rheumatoid arthritis was estimated. The studied parameters changed toward the control values after the test compound was injected into animals with the pathology, which could be explained by manifestation of its cardioprotective and antioxidant activities. The obtained data could be used to develop new methods for prevention and treatment of this pathological condition.

Reference standards, including pharmacopoeial reference standards, are widely used for quality assessment of drug substances. Leading global pharmacopoeias contain monographs regulating the requirements for the classification, attestation, and use of reference standards. The drug standardization system in the Russian Federation, which includes drug substances, requires revision for the creation and attestation of national reference standards, including pharmacopoeial ones.

The present study was aimed to optimize the conditions of Codonopsis pilosula desulfurization using orthogonal experiment analysis with four independent variables including desulfurization temperature, time, ultrasonic power, and ratio of ethanol to raw material. Aspects of the antibacterial activity of polysaccharides extracted from sulfur-fumigated C. pilosula and after desulfurization by the agar-well diffusion method against Escherichia coli have also been studied. The results showed that the optimum extraction conditions were as follows: desulfurization temperature, 45°C; desulfurization time, 50 min; ultrasonic power, 700 W; and ethanol to raw material ratio, 10 : 1. Under these conditions, the desulfurization rate was 55.4%. The antibacterial activity of polysaccharides extracted from desulfurized C. pilosula was higher than that of polysaccharides extracted from sulfur-fumigated herbs, with the MIC values of 35 and 70 mg/mL, respectively.

Medicinal plants are widely used for pharmacological agents. These herbs are very rich sources of bioactive compounds. Securigera securidaca is reputed in folk medicine as antidiabetic and antilipidemic drug. In this research, the effect of solvent’s polarity in bioactive extract of this plant was evaluated by GC/MS analysis. Then, hypoglycemic and hypolipidemic activities of different extracts were studied in diabetic rats and compared to glibenclamide.The results showed that carbon tetrachloride extract of this plant has the best and significant activity for reducing of glucose and lipid levels compared to other extracts because of higher content of sterols and fatty acids.

Implementation of new technologies for synthesizing drug substances, e.g., continuous-flow microreactor synthesis of active drug substances (ADS) and asymmetric synthesis of intermediates and ADS using enzymes created by gene engineering methods, is highly significant for localizing ADS production in Russia. The possibility of using the existing Russian scientific infrastructure for rapid implementation of domestic production of a new ADS portfolio with the least operating losses, maximum economic efficiency, and high competitiveness was demonstrated.

This review considered international approaches to assessment of the content of genotoxic impurities (residual solvents and various inorganic and organic impurities) in drugs. Foreign and domestic regulations defining requirements for the classification, control, and toxicological risk assessment of potential genotoxic impurities in drug substances and drugs were compared. The use of highly sensitive and specific analytical methods for detecting genotoxic impurities in drugs was justified. The need to improve the domestic regulatory framework on the control of elemental genotoxic impurities (heavy metals) and to prepare guidelines on the assessment of potentially genotoxic organic impurities in drugs was demonstrated.