Introduction. Epilepsy is one of the most common neurological diseases. The development of new, more potent and safe antiepileptic drugs remains an important task. Objective of the study. Evaluation of potential anticonvulsant effects of temgicoluril in average therapeutic doses in animal models of primary generalized epilepsy induced by corazol and maximum electric shock.
Objective. Evaluation of potential anticonvulsant effects of temgicoluril at average therapeutic doses in animal models of primary generalized epilepsy induced by corazole and maximum electroshock.
Materials and methods. Reproduced the corazolum (pentylenetetrazole) model in rats, and the maximum electric shock test (MES) in mice. For each experimental model of seizures, we subdivided the animals (42 mice and 42 rats) into 7 groups of 6 animals each. Group 1 was the control group; in groups 2, 3 and 4 animals were treated solely with temgicoluril at three doses of 10 mg/kg, 50 mg/kg and 100 mg/kg; in groups 5, 6 and 7 the animals were treated with reference antiepileptic drugs (bromdihydrochlorphenylbenzodiazepinum (2 mg/kg), valproic acid (400 mg/kg), and levetiracetam (54 mg/kg)). To the fnimals of control groups we administered equivalent amounts of distilled water. We administered all the studied drugs intraperitoneally within 30 minutes of the commencement of the experiment. To assess the reliability of the differences in samples having normal distribution, the parametric Student’s t-test was used.
Results. In the corazole model in rats, intraperitoneal administration of temgicoluril at a dose of 10 mg/kg, 50 mg/kg and 100 mg/kg did not affect the number of seizures, but temgicoluril significantly reduced the duration of a seizure relative to the control (17±2.84): at a dose of 10 mg/kg by 5.6 times (3.2±0.1): at a dose of 50 mg/kg — by 6.2 times (2.7±0.4), and at a dose of 100 mg/kg by 8.9 times (1.9±0.2) (p ≤ 0.05). Temgicoluril at doses of 10 mg/kg and 50 mg/kg completely prevented death of rats in the corazole model of seizures. Animal mortality was observed only in the group that received temgicoluril at a dose of 100 mg/kg, which was 33.3 % (n = 2) and did not differ from the control group — 33.3 % (n = 2). In the maximum electric shock test on mice, temgicoluril at doses of 10, 50 and 100 mg/kg showed an anticonvulsant effect similar to the effect of reference drugs (bromdihydrochlorophenylbenzodi azepine, valproic acid and levetiracetam): temgicoluril completely stopped seizures caused by MES. Accordingly, such parameters as the latent period, the number of seizures, the duration of seizures and mortality were zero, in contrast to the control group.
Conclusion. Temgicoluril in average therapeutic doses (10, 50 and 100 mg/kg) showed anticonvulsant activity in models of primary generalized epilepsy induced by corazole or maximum electric shock in animals (rats, mice).

Background. Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that play a key role in regulating both physiological and pathological processes in humans, particularly in oncological diseases. MMP-2 (gelatinase A) overexpression promotes metastatic progression in tumor cells. The development of selective MMP inhibitors as anticancer agents represents a promising approach in modern pharmacology. Previously, the compound 1-({4-[(4-chlorobenzoyl)amino]phenyl}sulfonyl)-L-proline, which received the laboratory code AL-828, was designed and synthesized using the pharmacophoric approach, possessing inhibitory activity against MMP-2.
Objective. Antitumor and antimetastatic activity of AL-828 compared with gemcitabine as the first-line antitumor drug.
Methods. This study was conducted on an experimental model of Lewis lung carcinoma (LLC) in C57BL/6 mice. AL-828 was administered intraperitoneally (i.p.) at doses of 10 and 30 mg/kg from day 1 to day 14 of tumor development. The antitumor drug gemcitabine was administered intraperitoneally as a reference drug at a dose of 50 mg/kg on days 2 and 9 of tumor development. The antitumor effect was assessed on days 7, 9, 15, and 21 of tumor development, and the metastasis inhibition index (MII) was measured on day 21 of tumor development. In this study, the average lifespan and survival rates were measured. Survival analysis was performed using the Kaplan–Meier method.
Results. AL-828 at doses of 10 and 30 mg/kg did not cause inhibition of tumor growth (ITG), whereas gemcitabine at a dose of 50 mg/kg significantly reduced tumor growth at all stages of registration at the level of 60 %. AL- 828 at a doses of 10 and 30 mg/kg, AL-828 showed antimetastatic effects, with MII values of 48.3 % and 39.2 %, respectively. Gemcitabine showed an MII of 75.8 %. Lungs from 50 % of the control group exhibited both light and high colonization potential with metastases. In contrast, the administration of either gemcitabine or AL-828 resulted in only light colonization potential in 90 % of treated animals.
Conclusion. Systemic course administration of AL-828 demonstrated antimetastatic activity in a model of LLC.

The aim of the study was to evaluate the pharmacodynamic equivalence of the drugs Antareit® (oral suspension, 800 mg/10 ml; Valenta Pharm JSC, Russia) and Riopan® (chewable tablets, 800 mg; Takeda GmbH, Germany) based on their antacid activity.
Material and methods. An open-label, two-period two-sequence crossover study was conducted to evaluate the pharmacodynamics of the test drug Antareit® (oral suspension, 800 mg/10 ml) and the reference drug Riopan® (chewable tablets, 800 mg), both administered as a single oral dose of 1600 mg. A total 50 healthy volunteers were randomized into two groups (n = 25) according to treatment sequence with a 7-day washout period between administrations. Gastric pH was continuously monitored for 1 hour after dosing using an intragastric pH probe placed in the gastric corpus. The main pharmacodynamics parameter was the area under the pH-time curve above baseline (AUCABL). Equivalence was determined by calculating the 90 % confidence interval (CI) for the ratio of marginal means of AUCABL between the two formulations. Safety was assessed through monitoring of adverse events (AEs), physical examinations, vital signs measurement, laboratory tests and electrocardiogram (ECG) findings.
Results. A total of 48 out of 50 randomized subjects completed both periods of the study. Two volunteers discontinued before receiving the drug in period 2. The 90 % CI for the AUCABL was calculated using a mixed-effects model (MIXED) and a generalized linear model (GLM). The marginal mean AUCABL values were 68,81 for Antareit®, oral suspension, 800 mg/10 ml and 68,42 for Riopan®, chewable tablets, 800 mg based on GLM analysis. The AUCABL ratio (test drug / reference drug) was 100,57 % (90 % Cl: 82,44–122,69 %), indicating non-inferiority. Three AEs occurred in two subjects: two cases of rhinorrhea in one volunteer and one case of somnolence following drug administration. There were no statistically significant differences in the frequency of AEs between treatments.
Conclusion. The study established pharmacodynamic equivalence between the test drug Antareit®, oral suspension, 800 mg/10 ml and the reference drug Riopan®, chewable tablets, 800 mg. The safety profiles of both treatments were found to be similar, with no significant differences observed in either the incidence or severity of AE.

Background. Metoprolol is a selective beta-blocker that is most commonly used in the pharmacotherapy of cardiovascular diseases, including hypertension (AH).
Objective. To evaluate the pharmacokinetics of metoprolol tartrate in patients with controlled and uncontrolled AH.
Materials and methods. An open cohort study was conducted at the Hospital Therapy Department of the Ryazan State Medical University in the Ryazan Regional Clinical Cardiology Dispensary. The study included 45 patients, including 29 with uncontrolled AH and 15 with controlled AH. All patients regularly take any two antihypertensive drugs (AHD) (lisinopril, amlodipine, and metoprolol tartrate) along with indapamide for a month. In the morning before and 2 h after taking metoprolol, venous blood samples were collected to assess the concentration of the analyzed substance (C0h and C2h, respectively) using high-performance liquid chromatography with tandem mass spectrometry.
Results. Analysis of C0h and C2h of metoprolol tartrate did not show statistically significant differences in patients with controlled and uncontrolled AH. In 93 % of patients, C0h and in 57.8 %, C2h were below the lower limit of the therapeutic range, without statistically significant differences in controlled and uncontrolled AH. The median daily dose of metoprolol tartrate was 50 (25; 75) mg, which is insufficient according to the AH guidelines (the recommended dose is 100 mg).
Conclusion. Thus, the pharmacokinetics of metoprolol tartrate did not make a significant contribution to achieving blood pressure control. In most cases, metoprolol tartrate concentration is below the therapeutic range, which is associated with a low drug dose.

Actuality. Bioimpedancemetry allows the assessment of the body’s components and has virtually no negative consequences. Using the presented method, the authors proposed approaches designed to reduce the clinical trial sample’s pharmacokinetic heterogeneity. This is dictated by the results of previous studies that showed that routine clinical, laboratory, and instrumental indicators do not allow the selection of subjects with an initially lower variability of pharmacokinetic parameters.
Objective. This study aimed to assess the possibility of using data obtained during a screening examination and the bioimpedancemetry method to identify subjects with an initially lower level of pharmacokinetic parameter variability during a highly variable raltegravir clinical trial (n = 50).
Methodology. A four-period study of a highly variable raltegravir was conducted in 2024 in accordance with the Russian Federation’s regulatory and ethical requirements. Mathematical and statistical analyses of the results were performed using the R 4.4.3 and Statistica 10.0 packages, as well as Microsoft Excel 2013 for plotting graphs and tables. A staged assessment of the information content of several parameters measured as part of routine medical manipulations, measurements of raltegravir plasma concentration parameters, and bioimpedancemetry parameters was performed.
Results. The results of a two-stage analysis of the parameters of volunteers who used raltegravir in a clinical trial allowed us to establish that the use of bioimpedancemetry results in addition to the clinical and laboratory parameters obtained during the screening period significantly increases the efficiency of discrimination of subgroups with different levels of variability in the training sample from 82.1% (total group and subgroups) to 97.2% in the total group and up to 100% in the variable pharmacokinetics subgroup.

The pharmacokinetics of ADK-1113 were studied in mice treated with different dosage regimens.
Objective. This study aimed to investigate ADK-1113 pharmacokinetics after multiple intraperitoneal administrations.
Methods. This study was conducted on male outbred mice. The concentrations of ADK-1113 in the blood plasma were determined using high-performance liquid chromatography with mass-spectrometric detection. The pharmacokinetic parameters were evaluated using a model-independent method.
Results. The test substance in the blood plasma was determined for 4 h after single and multiple (four times with a dosage interval of 2.8 h) intraperitoneal administrations at a dose of 10 mg/kg. ADK-1113 administration mode did not affect its half-life or mean residence time. ADK-1113 did not accumulate in mice.