ПО

П. О. Бочков

Russian Medical Academy of Continuous Professional Education

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i-10 index

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Co-Authors

ВП

В. П. Жердев

Medical Technologies (Czechia)

РВ

Р. В. Шевченко

Ministry of Health

АА

А. А. Литвин

Medical Technologies (Czechia)

ГБ

Г. Б. Колыванов

Medical Technologies (Czechia)

ОГ

Оксана Геннадьевна Грибакина

Medical Technologies (Czechia)

ДА

Д. А. Сычев

Russian Medical Academy of Continuous Professional Education

КБ

К. Б. Мирзаев

Russian Medical Academy of Continuous Professional Education

O. Yu. Kravtsova

Medical Technologies (Czechia)

Smirnov Vv

Sechenov University

КА

К. А. Акмалова

Russian Medical Academy of Continuous Professional Education

Cooperative Institutions

Russian Medical Academy of Continuous Professional Education

Ministry of Health of the Russian Federation

Russian Academy of Sciences

Sechenov University

Ministry of Health

Institute of Pharmacology Russian Academy of Medical Sciences

Academy of Medical Sciences

Peoples' Friendship University of Russia

City Clinical Hospital

Institute of Pharmacology

Author Statistics

Papers

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Absolute bioavailability of a substance with cardioprotective activity (ALM-802) in rats

Pharmacokinetics and Pharmacodynamics (2022)

Г. Б. Колыванов П. О. Бочков А. А. Литвин Р. В. Шевченко A. L. Podolko

The pharmacokinetics of a new potential cardioprotective agent ALM-802 was studied in rats after single intravenous and intragastric administration at doses of 10 and 100 mg/kg, respectively. The absolute bioavailability was 4.45 %, which indicates the potential for the development of a dosage form for oral administration

10.37489/2587-7836-2021-2-31-35

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Фармакокинетическая оценка пролонгированной лекарственной формы афобазола в сравнении с таблетками препарата, выпускаемыми промышленностью

Экспериментальная и клиническая фармакология (2013)

П. О. Бочков А. А. Литвин Г. Б. Колыванов В. П. Жердев Евгения Викторовна Блынская

Afobazole pharmacokinetics upon oral administration of tablets prepared according to various technologies was studied in rabbits. The main pharmacokinetic parameters were determined.

10.30906/0869-2092-2013-76-11-33-35

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Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice

Free Radical Biology and Medicine (2023)

С. С. Лебедев Mikhail Tavobilov А. А. Карпов K. A. Abramov П. О. Бочков

10.1016/j.freeradbiomed.2023.08.012

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Preclinical and Clinical Pharmacokinetics of a Novel Dipeptide Anxiolytic GB-115

Proceedings for Annual Meeting of The Japanese Pharmacological Society (2018)

П. О. Бочков Лариса Геннадьевна Колик В. П. Жердев Gennadiy B Kolyvanov A. Litvin

Background. A novel dipeptide GB-115, designed and synthesized in the "Zakusov Research Institute of Pharmacology", as an analogue of endogenous cholecystokinin-4, produced pronounced anxiolytic properties in different rodent models without adverse effects typical to benzodiazepines. Based on preclinical pharmacodynamic/pharmacokinetic results for clinical studies was recommended a tablet formulation. The aim of this study was to evaluate GB-115 pharmacokinetics in rats, rabbits and volunteers.

Pharmacodynamics

Preclinical research

Neurotransmitter Systems

10.1254/jpssuppl.wcp2018.0_po1-11-9

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Determination of a novel anticonvulsant drug GIZh-290 in rat plasma by liquid chromatography–tandem mass spectrometry

Pharmacokinetics and Pharmacodynamics (2022)

П. О. Бочков I. P. Khrustova А. А. Литвин Г. Б. Колыванов Р. В. Шевченко

GIZh-290 is a new derivative of 4-phenylpyrrolidone, based on the structures of racetams that combine anticonvulsant and nootropic effects. The method of high-performance liquid chromatography with mass spectrometric detection was developed and validated for the quantitative determination of a new potential anticonvulsant compound GIZh-290 in rat blood plasma. For the extraction of the analyte, liquid-liquid extraction with diethyl ether was used. The method was validated based on its selectivity, linearity, accuracy, precision, and stability. The linearity of the method was confirmed by a high correlation coefficient of 0.999. The percent recovery of GIZh-290 from blood plasma was 79.2 %. The intra- and inter-batch accuracy were 19.32 and 12.14 %. It was found that blood plasma samples containing GIZh-290 can be stored at ambient temperature during the working day.

Diethyl ether

10.37489/2587-7836-2021-2-3-10

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Фармакокинетика дипептидного миметика BDNF ГСБ-106 у крыс

Pharmacokinetics and Pharmacodynamics (2019)

В. П. Жердев Г. Б. Колыванов А. А. Литвин П. О. Бочков Оксана Геннадьевна Грибакина

Pharmacokinetics of the GSB-106 in variety of administration ways in rats was studied. After single oral administration the test substance was determined for 4 h in the blood plasma. Half-life was 0.65 h. The GSB-106 tissue availability in high-vascularized organs (liver, kidney, spleen) was over then skeletal muscle. In brain (target-organ) that parameter was 0.05. In the 24-hour urine the parent compound was not detected and in the feces were determined of 0.0001 % GSB-106 after oral administration in dose 150 mg/kg. The absolute bioavailability of GSB-106 was 5.6 %.

10.24411/2587-7836-2019-10038

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IMPACT OF ABCB1 AND CES1 GENETIC POLYMORPHISMS ON TROUGH STEADY-STATE DABIGATRAN CONCENTRATIONS IN PATIENTS AFTER ENDOPROSTHESIS OF KNIFE JOIN

Aterotromboz = Atherothrombosis (2018)

Д. А. Сычев А. Н. Леванов Tatiana Shelekhova П. О. Бочков Н. П. Денисенко

Oral anticoagulants are widely used to prevent thromboembolic events in patients following total knee arthroplasty [1]. The genetic characteristics of patients affect the efficacy and safety of anticoagulants [2]. Dabigatran etexilate is a direct inhibitor of thrombin used as a prophylaxis of venous thromboembolic events (VTE) in Europe and Russia. [3]. This study evaluated the impact of ABCB1 and CES1 genetic polymorphisms on the peak and residual dabigatran concentration in orthopedic patients. Material and methods: A total of 30 patients aged 43 to 77 years following knee joint replacement were enrolled in the study. All patients received dabigatran etexilate at a dose of 220 mg/day for the prevention of VTEO. ABCB1 and CES1 genetic polymorphism genotyping was performed by real-time polymerase chain reaction (PCR). The peak and residual concentrations of dabigatran were determined by high-performance liquid chromatography (HPLC). Results: It was found that the ТТ genotype of the MDR1 gene С3435Т polymorphism is associated with a higher peak concentration of dabigatran than the CC genotype (p <0.1). Statistically significant results for CES1 gene rs2244613 polymorphism were obtained in patients younger than 60 years (p <0.05). The analysis of the haplotypes combination in two polymorphisms showed that the most common haplotype combination CC (rs1045642) ABCB1/CT (rs2244613) CES1 was significantly associated with a higher peak concentration of dabigatran compared to the rest of haplotype combinations (p = 0.002). Conclusions: The examination of a cohort of patients receiving dabigatran for the prevention of VTE during the period of large joints arthroplasty showed that SNPs C3435T ABCB1 and rs2244613 CES1 could play an important role in changing dabigatran concentrations. No data suggestive of the impact of SNP ABCB1 rs4148738 on the peak concentration of dabigatran were received.

10.21518/2307-1109-2018-1-122-130

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Exome-Wide Association Study of candidate pharmacogenes on DOAC haemorrhage

Д. А. Сычев Anastasiia A. Buianova Sh. P. Abdullaev К. Б. Мирзаев Vera Belova

Background/Objectives: Direct oral anticoagulants (DOACs) are first-line medications for stroke prevention in non-valvular atrial fibrillation (AF). However, variability in drug response poses risks of hemorrhagic or thromboembolic events. The role of genetics in determining DOAC safety is gaining attention, but evidence linking specific genetic polymorphisms to bleeding risk is lacking. Therefore, the aim of our study was to conduct an Exome-Wide Association Study with 198 non-valvular AF patients treated with rivaroxaban or apixaban, including 97 with bleeding complications and 99 without. Methods: DOAC plasma concentrations, 6-β-hydroxycortisol and cortisol levels in urine were measured for CYP3A4 phenotyping. Sequencing was performed on the DNBSEQ G-400 platform. Single nucleotide variants (SNV) associations with bleeding risk were assessed using logistic regression with additive, dominant, and recessive genetic models. Results: No SNVs reached Bonferroni-corrected significance in any genetic model. Polygenic risk scores (PRS) showed weak predictive ability for bleeding with apixaban. For rivaroxaban, regression indicated that ln Css min/D + 1 index increased with PRS, age, and 6-β-hydroxycortisol/cortisol ratio, but decreased with higher 6-β-hydroxycortisol and coronary heart disease presence. Conclusions: The findings revealed that the residual equilibrium concentration of anticoagulants, including dose-adjusted, cannot alone predict bleeding risk in non-valvular AF patients. No new genetic variants associated with bleeding risk were identified.

Association (psychology)

Exome

10.20944/preprints202409.0734.v1

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Impact of CYP2D6 polymorphisms on the pharmacokinetics, efficacy, and safety of tamsulosin therapy in patients with benign prostatic hyperplasia

Meditsinskiy sovet = Medical Council (2025)

Sh. P. Abdullaev Sh. P. Abdullaev М Н Шатохин A. V. Krasnov П. О. Бочков

Introduction . CYP2D6 is involved in the metabolism of tamsulosin, which is used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). However, the impact of carrying polymorphic variants of the CYP2D6 gene on the clinical efficacy and safety of tamsulosin therapy is still not well understood. Aim. To evaluate the impact of CYP2D6 polymorphic variants on steady state concentration of tamsulosin (Css min ), as well as their correlation with the efficacy and safety of therapy in patients with BPH. Materials and methods . A single-center prospective study included 75 patients who completed all stages of the study. The median age of the patients was 69 years, body mass index was 27.17 ± 4.86 kg/m². 56 patients (74.67%) had comorbidities, which means the presence of at least one chronic disease in addition to the diagnosis of benign prostatic hyperplasia. 26 people (34.67%) were classified as polymorbid patients, i.e. having several comorbidities at once, while 19 patients (25.33%) had no comorbidities except for benign prostatic hyperplasia. Genotyping was performed by real-time polymerase chain reaction. Css min of tamsulosin was determined by HPLC-MS/MS. Efficacy of therapy was assessed using IPSS score and Qmax. Safety was assessed based on the incidence of adverse reactions. Results. Carriage of CYP2D6*4 and CYP2D6*10 was found to be associated with statistically significant increases in Cssmin levels. However, the identified pharmacokinetic differences, carriage of CYP2D6 markers was not reflected in the clinical efficacy and safety of tamsulosin. Conclusion. CYP2D6*4 and CYP2D6*10 may affect the Css min levels of the tamsulosin, but does not affect the clinical results of treatment.

Tamsulosin

10.21518/ms2024-478

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Pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in rats. Part 1. Single and multiple intravascular and extravascular administration. Testing the hypothesis of linearity of pharmacokinetics

Pharmacokinetics and Pharmacodynamics (2023)

O. Yu. Kravtsova Оксана Геннадьевна Грибакина Г. Б. Колыванов А. А. Литвин П. О. Бочков

The pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in the rat blood plasma after diﬀerent routes of administration was studied. The drug was administered at dose of 150 mg/kg by single and repeatedly. After single intravenous and intraperitoneal injection, GC-2 was detected for 2 h, its half-life was 0.4 h. GC-2 absolute bioavailability after single intraperitoneal injection was 84.62 %, that indicates the prospect of development its injectable (intramuscularly) dosage form. After 4-fold (1.5 h dosing interval) intraperitoneal injection dose-independent pharmacokinetic parameters of GC-2 practically do not change compared to single administration. This indicates that GC-2 is not accumulated in the body of rats. The hypothesis of the linearity of the pharmacokinetics of GC-2 in the rats blood plasma after single intraperitoneal administration at doses of 50, 100 and 150 mg/kg was tested. It was found that the kinetics of GC-2 in the rat blood plasma is linea.

Intraperitoneal injection

10.37489/2587-7836-2023-3-12-18

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