This report explores the antioxidant interaction of combinations of flavonoid–glutathione with different ratios. Two different 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS^•+)-based approaches were applied for the elucidation of the antioxidant capacity of the combinations. Despite using the same radical, the two approaches employ different free radical inflow systems: An instant, great excess of radicals in the end-point decolorization assay, and a steady inflow of radicals in the lag-time assay. As expected, the flavonoid–glutathione pairs showed contrasting results in these two approaches. All the examined combinations showed additive or light subadditive antioxidant capacity effects in the decolorization assay. This effect showed slight dilution dependence and did not change when the initial ABTS^•+ concentration was two times as high or low. However, in the lag-time assay, different types of interaction were detected, from subadditivity to considerable synergy. Taxifolin–glutathione combinations demonstrated the greatest synergy, at up to 112%; quercetin and rutin, in combination with glutathione, revealed moderate synergy in the 30–70% range; while morin–glutathione appeared to be additive or subadditive. In general, this study demonstrated that, on the one hand, the effect of flavonoid–glutathione combinations depends both on the flavonoid structure and molar ratio; on the other hand, the manifestation of the synergy of the combination strongly depends on the mode of inflow of the free radicals.

INTRODUCTION. Syrups are an important dosage form used in medical practice, particularly in paediatrics. As of January 2024, there are 212 medicinal products formulated as syrups approved in the Russian Federation. The effi­cacy, safety, and quality of syrups are determined by their composition, including excipients.AIM. This study aimed to analyse and systematise data on the role and safety of excipients in syrups included in the Russian State Register of Medicines.DISCUSSION. This article reviews the major groups of excipients present in syrups, including sweeteners, preservatives, solvents, thickeners, pH modifiers, buffering agents, antioxidants, and colourants. The most prevalent group of excipients is sweeteners, including sucrose (66.51%), sorbitol (29.25%), and sodium saccharin (10.85%). Sucrose contributes to tooth decay and is contraindicated in patients with diabetes and obesity. Sorbitol may cause gastrointestinal disorders. Data on the long-term safety of artificial sweeteners are contradictory. Therefore, sweeteners should be selected rationally. The most widely used preservatives are parabens, including methylparaben (31.60%) and propylparaben (20.28%). Propyl­paraben exhibits potential oestrogenic activity, which makes methylparaben the para­ben of choice. Solvents and co-solvents include water, glycerol (25.94%), ethanol (24.53%), and propylene glycol (20.75%). Ethanol and propylene glycol can cause severe central nervous system disorders. The most commonly used thickener is hydroxyethyl cellulose (5.19%). Cellulose derivatives are considered safe but may have a laxative effect if consumed in excess. The most popular colourant is Sunset Yellow (7.54%). The lack of data on the safety of many colourants emphasises the need for their rational selection.CONCLUSIONS. By analysing summaries of product characteristics and patient information leaflets for syrups available in the Russian State Register of Medicines, the authors have systematised data on the role, safety, and acceptable daily intake of excipients in used syrups, classified these excipients, and calculated the frequency of their use. The findings suggest that the current approaches to selecting excipients for syrups should be revised to minimise potential risks and to enhance the safety of medicinal products.

Фармакогенетические подходы к повышению эффективности и безопасности применения статинов на примере аторвастатина

The aim of the study was to review literature data on cell models for experimental assessment of drug nephrotoxicity in vitro. Because of nephrotoxicity, 2% of new investigational medicinal products are discarded at the stage of preclinical in vivo studies in laboratory animals, and 19%—after phase 3 clinical trials. Prediction of toxicity in cell models could make drug development more cost-effective and help to reduce/avoid animal testing. At present, there are no official international guidelines for assessment of nephrotoxicity in vitro, but there is a lot of research underway. The main toxicity target in kidneys is renal proximal tubule epithelial cells, therefore the main research is focused on the development of renal proximal tubule epithelial cell lines with stable functional characteristics. Another important aspect in nephrotoxicity modeling is the choice of relevant test methods and end points which would reflect potential toxicity mechanisms. The paper reviews existing human renal proximal tubule epithelial cell lines and current test methods for assessing cytotoxicity. Promising areas for future development of cell models for nephrotoxicity assessment— are optimisation and standardisation of in vitro systems that would help to make preclinical predictions of drug nephrotoxicity in vivo.

Organic anion transporters OAT1 and OAT3 play a key role in elimination of most β-lactam antibiotics. Since nonsteroidal anti-inflammatory drugs, antivirals, antitumor agents, and some other drugs are also substrates of OAT1/3, this enables drug-drug interaction (DDI). The aim of the study was to analyze scientific literature to determine the likelihood and significance of β-lactam antibiotic DDI mediated by organic anion transporters, as well as potential for predicting it. In clinical practice, inhibition of β-lactam antibiotic elimination is used to increase systemic exposition and reduce the cost of antibiotic therapy. OAT inhibitors (cilastatin, betamipron) are used in combination drugs to reduce nephrotoxicity of carbapenems. On the other hand, an increase in the concentration of β-lactams due to OAT inhibition may lead to adverse drug reactions. Therefore, the European Medicines Agency and the Food and Drug Administration recommendations for the development of new drugs state that in the case of significant renal excretion (≥25%) it is necessary to investigate OAT1/3 transportin vitroand calculate inhibition constantK_iand/or half maximal inhibitory concentrationIC₅₀for predicting DDI. One of the main problems is the variability ofK_i andIC₅₀ values between laboratories, which requires the development of general recommendations for different transporters as regards methods of determination of these parameters.