Background: Through measurements of the heart rate variability (HRV) accompanied by the pertinent biomarker assays, the effects of nicotine and byproducts derived from alternative nicotine delivery systems (ANDS) on the autonomic nervous system (ANS) and hormonal system have been investigated. Methods: HRV was studied in a group of volunteers (17 people), involving non-smokers, i.e., who never smoked before (11), ex-smokers (4) and active smokers (2). ANDS and smoking simulators, including regular, nicotine-free and electronic cigarettes; tobacco heating systems; chewing gums and nicotine packs of oral fixation (nic-packs), were used. Blood pressure, levels of stress hormones in saliva and catecholamines in the blood were also monitored. Results: HRV analysis showed relatively small changes in HRV and in the other studied parameters with the systemic use of nic-packs with low and moderate nicotine contents (up to 6 mg) compared to other ANDS. Conclusions: The HRV method is proven to be a promising technique for evaluation of the risks associated with smoking, dual use of various ANDS and studying the biomedical aspects of smoking cessation. Nic-packs are shown to be leaders in biological safety among the studied ANDS. A sharp surge in the activity of the sympathetic division of the ANS within the first minutes of the use of nicotine packs implies that nicotine begins to act already at very low doses (before entering the blood physically in any significant amount) through fast signal transmission to the brain from the nicotinic and taste buds located in the mouth area.

Vancomycin is prescribed to patients in serious condition with infections caused by Gram-positive microorganisms; however, if the therapeutic plasma concentration of the medicinal product is exceeded, it can have a nephrotoxic effect.The aim of the study was to demonstrate the possibility of using therapeutic drug monitoring (TDM) to reduce the risk of developing nephropathy in intensive care unit patients with sepsis.Materials and methods: the study comprised a retrospective analysis of four clinical cases of patients with sepsis admitted to intensive care units of I.V. Davydovsky City Clinical Hospital in 2021 and treated with vancomycin. TDM of vancomycin plasma levels was performed by reverse-phase high-performance liquid chromatography with mass spectrometric detection.Results: using the four cases of septic patients, the study demonstrated that vancomycin at adequate case-specific doses may result in plasma concentrations beyond the therapeutic range. TDM of vancomycin concentrations helped to prevent further deterioration of renal dysfunction in one septic patient having developed acute kidney injury and to control the achievement of therapeutic vancomycin concentrations or timely adjust the dose to that effect in the other three cases.Conclusions: a timely correction of vancomycin dosing with plasma TDM allows for achieving high antimicrobial efficacy in patients with sepsis and minimising the nephrotoxic effect of the medicinal product. Studies of the feasibility of using TDM as a treatment personalisation tool for patients in serious condition will continue in the future.

В повседневной практике врач, назначая лечение пациентам с инфекционными заболеваниями, руководствуется клиническими рекомендациями. Однако в них не учитывается ряд факторов,

Scientific relevance. Vancomycin and linezolid are the antibacterial agents of choice for severe infections caused by multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). However, few studies have been conducted in Russia to analyse the safety of these medicinal products.Aim. The study aimed to compare the safety of vancomycin and linezolid using the Moscow segment of the Russian Federal Service for Surveillance in Healthcare’s database for adverse drug reaction (ADR) reports.Materials and methods. The study used information from the spontaneous reporting database for 2018–2022, which contained 147 ADR reports for vancomycin (122 reports) and linezolid (25 reports). The authors analysed the ADR distribution and assessed the statistical significance of the identified differences by sex, weight, and age of patients, conditions of medical care, route of administration, single dose, daily dose, therapy duration, ICD-10 codes, ADR severity, and ADR outcome.Results. The distribution of adverse reactions to vancomycin and linezolid by patient age was relatively uniform. Outpatient linezolid was associated with a significantly higher rate of ADRs (3 of 5 reports) than outpatient vancomycin (21 of 129 reports; p=0.0408). For ADR severity, 5 of 20 ADRs reported with linezolid required hospitalisation or prolongation of hospitalisation—considerably more than with vancomycin (16 of 94 reports; p=0.528). The average single dose of vancomycin (794 mg) was higher than that of linezolid (467 mg; p=0.007); the same was noted for average daily doses (1273 mg vs 998 mg; p=0.3664). The mean duration of treatment with linezolid before ADR onset was 5.26 days, which was significantly longer than the mean duration of treatment with vancomycin (2.44 days; p=0.0053). Oral linezolid was associated with a significantly higher ADR rate (4 of 19 cases) than oral vancomycin (5 of 96 cases; p=0.0027).Conclusions. The ADRs observed with vancomycin and linezolid were predictable and class-specific. According to the results of the ADR report analysis, adverse reactions to vancomycin and linezolid were associated with different factors. Similar results of the literature analysis confirmed this conclusion. However, according to the results of the linear regression analysis, none of the factors considered in this study had a statistically significant influence on the probability of developing an adverse reaction to vancomycin or linezolid.

BACKGROUND: Levofloxacin concentrations do not always reach desired levels when administered at a standard dose; therefore, measuring levofloxacin levels in the blood plasma or other alternative matrices, such as the saliva, can help clinicians make informed decisions concerning the dosage and mode of administration. Saliva, as an object of research, is of particular interest due to the simplicity and non-invasiveness of sampling for analysis. AIM: This study aimed to determine the comparative pharmacokinetics of levofloxacin in the blood plasma and saliva of patients with community-acquired pneumonia (CAP) and assess the possibility of using saliva as an alternative sampling matrix in pharmacokinetic studies. MATERIALS AND METHODS: Levofloxacin concentration in the blood plasma and saliva of patients with CAP and volunteers was determined using high-performance liquid chromatography on an Agilent 1200 liquid chromatography (Agilent, USA) with an ultraviolet detector. Sample preparation of bioassays was performed using protein precipitation. Patients and volunteers took 1 tablet (500 mg dose) of levofloxacin per os in the morning, on an empty stomach. Blood and saliva samples were taken at the initial blood sample and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 h after taking the drug. The pharmacokinetic parameters were determined, namely Cmax as the peak concentration of the drug; Тmax as the time-to-peak concentration; AUC0t as the area under the pharmacokinetic curve in the range from 0 to the last experimental point on the curve; AUC0 as the total area under the pharmacokinetic curve from zero to infinity; t1/2 as half-life period; MRT as mean residence time of the drug in the blood (h); Cl/F as clearance; and Vss/F as the total distribution volume. RESULTS: The maximum blood plasma and saliva concentration of patients was reached 1 h after taking the drug and amounted to Сmax=5.982.89 g/ml and Сmax=4.413.83 g/ml, respectively. Additionally, the maximum concentrations in blood plasma and saliva were recorded 1 h after taking the drug as 5.523.07 g/ml and 3.250.85 g/ml, respectively, in healthy volunteers. The correlation coefficient (r) between the mean values of the levofloxacin concentrations in the blood plasma and the saliva of patients with CAP was 0.953 and that of healthy volunteers was 0.977. DISCUSSION: Pharmacokinetic parameters were calculated based on blood plasma and saliva concentrations. Their comparative analysis revealed almost the same absorption rate from the gastrointestinal tract in patients and healthy volunteers. Correlation-regression analysis revealed a high correlation between the average values of Cmax in saliva and plasma both in the patient (r=0.96) and healthy volunteer group (r=0.98). CONCLUSIONS: With statistically significant differences in the areas under pharmacokinetic curves in blood plasma and saliva, the remaining pharmacokinetic parameters of saliva and blood plasma did not significantly differ between patients with CAP and healthy volunteers. A significant direct correlation was revealed between the mean concentration and pharmacokinetic parameters in saliva and blood plasma in both groups. The study demonstrated the possibility of using saliva as a biomaterial in the study of levofloxacin pharmacokinetics.