The impact of , and gene polymorphisms on apixaban trough concentration and bleeding risk in patients with atrial fibrillation.

Objectives: Apixaban, a direct oral anticoagulant, is increasingly used worldwide for the treatment and prevention of venous thromboembolism and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Obviously, one of the ways to enhance effectiveness and safety of drug therapy is a personalized approach to therapy, which involves pharmacogenetic and pharmacokinetic tests. The study aims to investigate the effect of , and polymorphisms on the pharmacokinetics of apixaban and the risk of bleeding.

Pharmacogenetic markers of development of angioneurotic edema as a secondary side effect to enalapril in patients with essential arterial hypertension.

Background: Angioneurotic edema is the most dangerous complication in angiotensin-converting enzyme inhibitors (ACEIs) therapy. Based on the current data, the clinical and genetic predictors of angioedema development are still understudied, which demonstrates the relevance of this study.

Objective: To reveal the pharmacogenetic predictors of the angioedema as a secondary side effect to enalapril in patients with essential arterial hypertension.

A Systematic Review on the Safety of -Specific Antigen-Based Skin Tests for Tuberculosis Infection Compared With Tuberculin Skin Tests.

Background: A systematic review showed that the accuracy of antigen-based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of TBSTs has not been systematically reviewed.

Methods: We searched for studies reporting injection site reactions (ISRs) and systemic adverse events associated with TBSTs. We searched Medline, Embase, e-library, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure database for studies through 30 July 2021, and the database search was updated until 22 November 2022.

Pharmacogenetic predictors of development of secondary to enalapril dry cough in hypertensive patients.

Objectives: Development of the secondary to ACEI cough leads to discontinuation of the drugs of this group. Assessing the safety of the ACEIs with further development of customized approaches for their administration is a major scientific and practical problem. The objective of this study was to assess the association of the genetic markers with the development of the adverse drug reaction in the form of secondary to enalapril dry cough in the patients with essential arterial hypertension.

Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice.

Objective: The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation.

Methods: In total 86 patients (42 men and 44 female), aged 67.

The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation.

Introduction: ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial.

Aim: To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF).

Methods: 128 patients aged 80 years and older (median [Me] age 87.

Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied.

Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V was found for etacizine (+39 Δ%); there was an increasing trend in Cl for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH.

Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia.

Objectives: The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors.

Methods: Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40 mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH).

Influence of Clinically Significant Genes on Antiplatelet Effect of Clopidogrel and Clinical Outcomes in Patients with Acute Coronary Syndrome and Atrial Fibrillation.

Introduction: The interindividual variability of the antiplatelet effect of clopidogrel is determined by multiple clinical and genetic factors. A lot of genotype-oriented studies have concentrated on the impact of CYP2C19 gene polymorphisms on platelet aggregation in patients receiving clopidogrel. However, the influence of this polymorphism may be only 12-20%, so other genetic markers should also be investigated.

Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied.

Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V was found for etacizine (+39 Δ%); there was an increasing trend in Cl for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH.

SYmbicort given as needed in mild asthma (SYGMA study): a retrospective subanalysis of the Russian population.

Introduction: While mild asthma is generally better controlled than more severe disease, patients with mild asthma may experience severe exacerbations. Definite differences between countries in terms of asthma severity and control were described previously. Since SYGMA was a global study, this sub-analysis was conducted in geographic region to investigate potential regional specificities.

[Evidence-Based Information Which Could Influence Arterial Hypertension Treatment Approach after Publication of SPRINT Trial Results].

The article discusses results of secondary analysis of the data obtained in the SPRINT study and published in recent years. Unresolved issues in the tactics of managing patients with arterial hypertension are discussed. One of such issues is choosing an optimum level of blood pressure (BP) for a subgroup of patients with certain characteristics, including elderly and senile patients, patients with chronic kidney disease, and patients with arterial hypertension who continue smoking.

Drug-drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation.

Objectives For revealing the peculiarities of the drug-drug interaction of rivaroxaban (substrate CYP3A4 and P-gp) and calcium channel blockers (CCBs) (verapamil - inhibitor CYP3A4 and P-gp and amlodipine - substrate CYP3A4) in patients 80 years and older with nonvalvular atrial fibrillation (NAF) we studied 128 patients. Methods All patients were divided into groups depending on the therapy taken: the 1st - rivaroxaban + amlodipine (n=51), the 2nd - rivaroxaban + verapamil (n=30), the control group - rivaroxaban without CCBs (n=47). A trough steady-state plasma concentration (C min,ss) of rivaroxaban, prothrombin time (PT) in the blood plasma and the event of clinically relevant non-major (CRNM) bleeding were assessed for each patient.

Drug-drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation.

Objectives For revealing the peculiarities of the drug-drug interaction of rivaroxaban (substrate CYP3A4 and P-gp) and calcium channel blockers (CCBs) (verapamil - inhibitor CYP3A4 and P-gp and amlodipine - substrate CYP3A4) in patients 80 years and older with nonvalvular atrial fibrillation (NAF) we studied 128 patients. Methods All patients were divided into groups depending on the therapy taken: the 1st - rivaroxaban + amlodipine (n=51), the 2nd - rivaroxaban + verapamil (n=30), the control group - rivaroxaban without CCBs (n=47). A trough steady-state plasma concentration (C min,ss) of rivaroxaban, prothrombin time (PT) in the blood plasma and the event of clinically relevant non-major (CRNM) bleeding were assessed for each patient.

Factors Affecting Trough Plasma Dabigatran Concentrations in Patients with Atrial Fibrillation and Chronic Kidney Disease.

Introduction: Dabigatran is effective and widely used to prevent ischemic stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Chronic kidney disease (CKD) also has implications for choice of any medications, as it alters pharmacokinetic parameters of drugs.

Aim: To evaluate trough plasma dabigatran concentration (DTPC) and to analyse potential factors affecting these values in patients with AF and CKD.

Peculiarities of Pharmacokinetics and Bioavailability of Some Cardiovascular Drugs under Conditions of Antiorthostatic Hypokinesia.

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

Effect of CES1 and ABCB1 genotypes on the pharmacokinetics and clinical outcomes of dabigatran etexilate in patients with atrial fibrillation and chronic kidney disease.

Background Despite the well-studied safety profile of dabigatran, its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). The study assessed whether genetic factors can contribute to CKD and alter dabigatran concentration. Methods Patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110 or 150 mg have been included in the study.

Antihypertensive Effect Of Amlodipine In Co-Administration With Omeprazole In Patients With Hypertension And Acid-Related Disorders: Cytochrome P450-Associated Aspects.

Background: CYP2C19 and CYP3A are the main enzymes involved in omeprazole metabolism, while CYP3A is the principal enzyme family for amlodipine biotransformation. Concomitant use of these drugs in patients with hypertension and acid-related disorders (ARD) might lead to drug-drug interaction.

Purpose: The aim of the study was to find if adding omeprazole for treating ARD to amlodipine long-term therapy of hypertension influenced blood pressure of CYP2C19 polymorphism carriers.

An improved extraction protocol for therapeutic dabigatran monitoring using HPLC-MS/MS.

A new sample extraction protocol was developed for pharmacokinetic studies of dabigatran with high-performance liquid chromatography separation - electrospray ionization time-of-flight mass spectrometry analysis. After protein precipitation with acetonitrile, free dabigatran and its metabolites are separated into water phase by water-dichloromethane liquid-liquid extraction to purify the sample from proteins and endogenous lipophilic compounds. Chromatographic separation was achieved on an Agilent Zorbax SB-CN column (150 × 4.

[Pharmacogenetics of timolol].

In recent years, β-adrenergic blockers have become the first choice drugs for glaucoma treatment. Timolol holds the main position among them, being a part of most combined antiglaucoma preparations. The use of timolol maleate in clinical practice may be accompanied by severe side effects affecting different organs and systems.

Withdrawal of inhaled corticosteroids in COPD patients: rationale and algorithms.

Observational studies indicate that overutilization of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD). Overprescription and the high risk of serious ICS-related adverse events make withdrawal of this treatment necessary in patients for whom the treatment-related risks outweigh the expected benefits. Elaboration of an optimal, universal, user-friendly algorithm for withdrawal of ICS therapy has been identified as an important clinical need.

Experimental and Clinical Pharmacokinetics of Fluoxetine and Amitriptyline: Comparative Analysis and Possible Methods of Extrapolation.

The pharmacokinetics of two fluoxetine capsulated dosage forms and two amitriptyline tablet forms after a single oral intake was studied in dogs and healthy volunteers. High significant correlations were detected between plasma concentrations of fluoxetine (r=0.96, p<0.

Effects of polymorphisms on the efficacy and safety of amlodipine therapy in Caucasian patients with stage I-II hypertension.

Purpose: The aim of this study was to determine the impact of (MDR1) polymorphisms on the efficacy and safety of amlodipine in Caucasian patients.

Patients And Methods: The 12-week study included 100 patients. Patients with the newly diagnosed stage I-II hypertension (HT) were recruited to complete genotyping of the single-nucleotide polymorphism (SNP).