Bisoprolol Research Articles

Bisoprolol Fumarate: An Exploration on its Properties and Analytical Methods

Bisoprolol Fumarate: An Exploration on its Properties and Analytical Methods

Innovative Long-Acting Bisoprolol Patch: Synergistic Ion-Pair Skin Adsorption for Drug Delivery Control Coupled with Dynamic Modulation of Penetration Enhancers.

This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C6-C12) were chosen as counterions to precisely control BSP's permeation rate in the patch formulation, and the ion-pairing strategy's mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP's passive diffusion rate. Particularly, the BSP-C10 ion pair successfully reduced BSP's permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT0-t, halves Cmax, and significantly reduces the occurrence of blood pressure fluctuations.

Evaluation of β‐ and γ‐Cyclodextrins as Promising Bisoprolol Drug Carriers: Docking, Molecular Dynamics and MM‐PBSA1 Free‐Energy Calculations*

AbstractIn this research work, the binding mechanism of Bisoprolol (BIS) drug into the beta‐cyclodextrin (β‐CD) and gamma‐cyclodextrin (γ‐CD) nanopores were investigated using docking, molecular dynamics (MD) simulations, and MM‐PBSA free energy calculations. Also, we assessed the energetic aspects within the BIS‐CDs complex under different thermal conditions in four stages from 298 to 334 K, which includes mammalian body temperature in order to approximate physiological conditions. The computational results reveal that the encapsulation of the BIS into the cavities of CDs is reinforced by hydrogen bonds (HBs) and van der Waals (vdW) interactions in the aqueous phase. The stability of the inclusion complexes of β and γ‐CD with BIS was confirmed by evaluating system stability, flexibility, dynamic and thermodynamic properties at all temperature steps. Next, we analyzed the degree of complexation between BIS and CDs at four different temperatures. The findings revealed that the degree of complexation is decreased as the temperature is increased. The translational movement of the drug to the outside of the CDs cavity increased in the temperature range of 310 to 334 K in γ‐CD more than β‐CD. The β‐CD complex exhibits greater stability compared to the γ‐CD complex in the aqueous medium. The MM‐PBSA free energy approach also confirms more binding affinity of BIS drug into the β‐CD cavity. keywords: Bisoprolol, β‐cyclodextrin, γ‐cyclodextrin, Molecular dynamics, MM‐PBSA free energy.

Simple simultaneous analysis of various cardiovascular drug mixtures with vincamine: comparative eco-friendly assessment

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.

6923 Case Report: Long Standing Type 2 Diabetes with TOFI Phenotype Successfully Weaned Off One Hundred Units of Basal-Bolus Insulin Therapy With Glucagon-Like Peptide 1 Receptor Agonist Therapy

Abstract Disclosure: Y.C. Kon: None. A 60-year-old Indian male was diagnosed with type 2 diabetes in 1997. In July 2017, his fasting blood glucose level (FBGL) was 10.3 mM, paired C-peptide 719 pM, eGFR measured as more than 60 ml/min. Since Sep 2017, he had been compliant on the same stable regimen of sc insulatard 20 units om and 20 units at 10 pm, sc actrapid 20 units t.i.d premeal, PO metformin 850 mg t.i.d and PO dapagliflozin 10 mg om. In the past, he had suffered myocardial infarction, with left ventricular ejection fraction 35%, and had left anterior descending coronary artery stenting. In 2017, he had automatic cardioverter defibrillator implanted for primary arrhythmia prevention. His cardiac medications included bisoprolol fumarate 5 mg om, losartan 25 mg om, spironolactone 25 mg om, aspirin 100 mg om and high intensity statin therapy. Since 2020, his HbA1c had measured 8% to 9% with FBGL at 6 mM to 11 mM. Hence he was referred by his cardiologist in Oct 2022 to optimize glycaemic control. Once every few months, he experienced hypoglycaemic symptoms with corresponding low capillary blood glucose (CBG) of 3 mM, reversed with glucose intake. On physical examination, he weighed 81.6 kg, BMI was 25.4 kg/m2, BP 110/67 mmHg, pulse rate 69/min regular, waist circumference 106 cm. There was no acanthosis nigricans. He did not appear Cushingoid nor acromegalic. As he had “thin outside, fat inside (TOFI)” type 2 diabetes phenotype, he was started on sc liraglutide 1.8 mg om. His actrapid dose was halved to 10 units premeal, and insulatard dose halved to 10 units bid. His dapagliflozin was switched to subsidised empagliflozin 25 mg om. Subsequently, his premeal CBG measured 4 to 7 mM, bedtime CBG 4-6 mM, with occasional minor hypoglycaemic episodes with CBG at 3-4 mM. In July 2023, HbA1c measured 6.3%, FBGL was 5.5 mM and paired C-peptide measured as 554 pM. Basal insulatard was discontinued and he was switched from liraglutide to sc dulaglutide 1.5 mg once weekly. In Oct 2023, his FBGL was 5.2 mM and HbA1c had improved markedly to 5.7%. His weight had reduced from 81.6 kg to 70.0 kg, BMI decreased from 25.4 kg/m2 to 22.9 kg/m2 and waist circumference reduced from 106 cm to 97 cm. As he continued to experience occasional minor hypoglycemic episodes, actrapid insulin was discontinued. On his current therapy of sc dulaglutide 1.5 mg once weekly, PO empagliflozin 25 mg om, PO metformin 850 mg tid, and PO acarbose 50 mg t.i.d, his fasting CBG measured 6.7-7.7 mM, premeal CBG 6.4 to 10.1 mM, off all insulins and without further episodes hypoglycaemia. Conclusion: Patients with long standing “TOFI” type 2 diabetes and robust C-peptide may be trialled on GLP1-receptor agonist therapy to wean off high daily doses of insulin, thus avoiding hypoglycaemia, achieving weight and abdominal fat loss, whilst maintaining glycaemic control. This is especially important in patients with established coronary artery disease. Presentation: 6/3/2024

Three spectrophotometric quantitative analysis of bisoprolol fumarate and telmisartan in fixed-dose combination utilizing ratio spectra manipulation methods

Hypertension is a chronic condition with multiple drug regimens. Limiting these medicines is critical to patient compliance. Therefore, bisoprolol and telmisartan were recently developed in a fixed-dose combination to control blood pressure. The UV absorption spectra of bisoprolol and telmisartan overlapped significantly. Thus, three spectrophotometric methods have been developed for simultaneous determination of bisoprolol and telmisartan without prior separation. Method A is ratio difference of ratio spectra (RD), which measures the amplitude difference between (210–224) nm for bisoprolol and between (255–365) nm for telmisartan. Method B, the first derivative of ratio spectra (1DD), measures amplitude signals at 232 and 243 nm for bisoprolol and telmisartan, respectively. Method C is the mean centering of ratio spectra (MC), which measures the mean-centered ratio spectra's values at 223 nm for bisoprolol and 245 nm for telmisartan. The applied methods showed good linearity 2–20 µg/mL for bisoprolol, 4–32 µg/mL for telmisartan, with sufficient accuracy and precision. The methods were sensitive, with LOD values of 0.243 µg/mL and 0.596 µg/mL in RD method, 0.313 µg/mL and 0.914 µg/mL in 1DD method, and 0.406 and 0.707 µg/mL in MC method for bisoprolol and telmisartan, respectively, the methods were validated per ICH criteria. The novel methods are precise and accurate and can be used for routine analysis and quality control of bisoprolol and telmisartan in pure and dosage form. Furthermore, the greenness of the approaches was evaluated using Analytical Greenness assessment (AGREE), and the suggested method received a high greenness score.

Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate.

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson-Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer-Peppas models.

Cu-Co Bimetallic Catalyst-based Electrochemical Sensing Platform for Determination of Bisoprolol in Clinical Samples.

Bisoprolol (BIS) is a selective beta-blocker. It has been successfully used to treat hypertension and angina pectoris. An overdose of BIS can lead to serious complications. An overdose is a medical emergency that requires immediate medical attention to overcome the adverse effects of the overdose. Hence, sensitive, reliable, and cost-effective methods are required for the determination of BIS. In this work, a new electrochemical sensing platform based on a bimetallic catalyst was developed for the determination of BIS. The Cu-Co nanocatalyst was easily synthesized by galvanic displacement onto a carbon paste electrode (CPE). Then, field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), and cyclic voltammetry (CV) were utilized for the characterization of the Cu-Co catalyst. The galvanic displacement of Cu metal significantly affected the electro-catalytic behavior of the Cu-Co catalyst and the Cu-Co/CPE electrode displayed a very sensitive and accurate response towards BIS. Under optimized conditions, the response was linear in the 3 to 120 μM concentration range, sensitivity of 631.1 μA mM-1 and a detection limit of as low as 0.4 μM using cyclic voltammetry. The simple proposed method was also successfully employed in the analysis of BIS in biological and pharmaceutical samples. The advantages of Cu-Co/CPE are its fast and simple manufacturing and the possibility of a repeated surface regeneration of the sensing platform, as well as its application for the detection of BIS in tablets and biological samples, making Cu-Co significant promise for use in clinical diagnostics. Besides, the synthesized catalysts showed excellent reusability and stability. The presence of Cu metal due to galvanic displacement increased the sensitivity. These findings suggest that the new nanocatalyst has potential applications in sensors and electronics.

High-performance thin-layer chromatography-based methodology for simultaneous estimation of bisoprolol fumarate and telmisartan

High-performance thin-layer chromatography-based methodology for simultaneous estimation of bisoprolol fumarate and telmisartan

MICROENCAPSULATION BISOPROLOL FUMARATE WITH EUDRAGIT E PO BY SOLVENT EVAPORATION METHOD

Objective: This study aimed to develop and optimize the microcapsule formula of bisoprolol fumarate-Eudragit EPO by double-emulsion solvent evaporation.
 Methods: The preparation of bisoprolol fumarate-Eudragit EPO microcapsule was done in three different ratios 1: 3 (F1), 1: 4 (F2), and 1: 5 (F3), followed by characterization of each of the microcapsule formula using Fourier transform infrared, scanning electron microscopy, particle size analyzer. Further analysis included investigation of the drug loading, entrapment efficiency, solubility in pH 6.8, and the difference among dissolution profiles of each microcapsule using one-way ANOVA.
 Results: Infra-red spectrum showed no chemical interaction between bisoprolol fumarate and Eudragit E PO in microcapsules. The morphology and structure of F1 microcapsule was irregular spheres, while F2 and F3 were regular spheres. The average particle distribution of microcapsules was 24.765±0,236 μm (F1), 28.245±0,252 μm (F2), and 40.634±0,218 μm (F3). The drug loading was 7.691±0,087 % (F1), 8.922±0,056 % (F2), and 9.012±0,133% (F3). The encapsulation efficiency was 4.980 % (F1), 5.857%(F2), and 6,285 %(F3). The average amount of bisoprolol fumarate released in pH 6.8 was 2.113±0,289 % (F1), 1.954±0,015 % (F2), and 1.619±0,020 % (F3). The dissolution profile between each formula was statistically different (p value= 0,000).
 Conclusion: As the low value of drug loading and encapsulation efficiency in each formula, we concluded that the microencapsulation formula with Eudragit EPO by solvent evaporation method is not effective to entrap bisoprolol fumarate.

Effects of Fixed Orthodontic Appliance with Antihypertensive Drugs on the Body Weight of Experimental Rats

Background: This study aims to investigate the effect of fixed orthodontic appliances and/or antihypertensive drugs on the weight of experimental rats. Materials and Methods: Thir-ty-six male Wistar albino rats were subjected to a split-mouth design study, in which an orthodontic appliance was inserted in one side to move the first molar mesially for 2 weeks while the other side acted as a control to tooth movement. The rats were allocated into three groups: group A (n = 12), without any pharmacological treatment; group B (n = 12), subcu-taneous injection of bisoprolol fumarate (5 mg/kg) daily; and group C (n = 12), subcutaneous injection of valsartan (10 mg/kg) daily. A fixed orthodontic appliance with a closing coil spring delivering 50 gm of force was used to move the first molar mesially while the incisors served as an anchor unit. The weight of the rats was measured on days 1 (the day of appli-ance insertion), 7, and 14. Results: No significant (P > 0.05) difference in the body weight of rats was found among the three groups at each time point; however, significant (P < 0.05) weight loss was noted after the first and second week of the experiment in all study groups. Conclusion: The body weight loss of rats following the insertion of a fixed orthodontic ap-pliance could be related to the effects of the appliance rather than the administered antihy-pertensive drugs.

The improvement of routine drug quality control analysis of some antihypertensive drugs using high-performance thin-layer chromatography densitometry method with greenness profile evaluation.

The common antihypertensive drugs are B-blockers and diuretics. For the determination of beta-blocker medicines (bisoprolol fumarate and carvedilol) and diuretic drug (Furosemide), new and accurate chromatographic method has been developed. The separation was achieved using a developing system that includes chloroform:methanol:ethyl acetate:ammonia (6:2:2:0.2 by volume) as a mobile phase and the bands were detected at 240nm. The concentration ranges were 5-25, 1-7, and 1-3.5μg/band for bisoprolol fumarate, carvedilol, and furosemide, respectively. This chromatographic approach is the first methodology for simultaneously determining bisoprolol fumarate, carvedilol, and furosemide in their pure forms and in their pharmaceutical dosage forms. The advantages of using known analytical procedures are their simplicity, speed, cost effectiveness, lack of laboriousness, and ability to save time as the three tablets are determined in one step and can be used for routine analysis of the investigated combinations in quality control laboratories. According to International Conference of Harmonization guidelines, the established procedures have been validated, and the results were statistically compared to those obtained by the reported reversed-phase-high-performance liquid chromatography methods using Student's t-test and F-test, with no significant difference between them, indicating that the proposed methods can be used for routine drug quality control analysis.

Development and Validation of a Novel Analytical Method (Ion Pair HPLC) For Separating and Determining Bisoprolol Fumarate and Carvedilol in Pure and Their Pharmaceutical Forms.

This work shows a new analytical method (ion pair HPLC) for the analysis of Bisoprolol Fumarate (BIS) and Carvedilol (CAR) in bulk and tablet. The developed analytical method has been carried out on an Inertsil ODS-3 5µL column 4.6 X 250 mm (w), as stationary phase using a mobile phase {Acetonitrile/ water 50/50 (v/v) containing sodium heptane sulfonic salt 0.001M as Ion pair agent}. The detection wavelength was 223 nm and the flow rate was 1.5 mL /min. Retention times were 3.5 min of BIS and 5.8 min of CAR. The analytical method has been validated by ICH guidelines. The developed method gave linearity in the concentration range of 20–60 µg/ mL accuracy with mean recovery values between 98-102 % (99.73% for BIS and 101.2% for CAR). The developed method is useful for separating and determining Bisoprolol Fumarate and Carvedilol in their pharmaceutical forms.

Unilateral adrenalectomy for a drug-resistant bilateral primary aldosteronism with heart failure: pathophysiology and surgical indication

BackgroundPatients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy.Case presentationA 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient’s heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient’s heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment.ConclusionsUnilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.

Synthesis and characterization of related compounds of Bisoprolol fumarate: a β-blocker agent

Synthesis and characterization of related compounds of Bisoprolol fumarate: a β-blocker agent

Development, optimization and in vitro-in vivo evaluation of solid lipid microparticles for improved pharmacokinetic profile of bisoprolol

The current research aimed at designing and optimizing controlled release solid lipid microparticles (SLMs) of Bisoprolol (BPL) from biocompatible waxes by using Box-Bhenken design (BBD) for improving the drug pharmacokinetics, enhancing compliance in hypertensive patients as well as eliminating inefficiencies of traditional methods of drug delivery. Seventeen formulations (F1 to F17) of controlled release BPL loaded SLMs were made by melt emulsification technique where Carnauba wax (CW) and Ceresin wax (CSW) were used as carriers and Tween 80 was used as stabilizer. The SLMs were characterized using fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Results revealed that micromeritics properties of all SLMs were satisfactory and showed good percentage yield (PY) and entrapment efficiency (EE). The minimum EE was observed by formulation-1 (F1) as 21.66% whereas F3 has showed maximum EE as 88%. Results of in vitro release study revealed that all formulations showed a well-controlled release in simulated intestinal medium at pH 7.4. The formulation F3 with high wax concentration revealed best extended release characteristics (29%) in 12 h. The pharmacokinetics studies of SLMs demonstrated an expressively lower Cmax (maximum plasma concentration) of BPL (53.61 ± 2:52) with a satisfactorily higher time to achieve maximum plasma concentration (Tmax) of 10.24 h as compared to Cmax (79.63 ± 5.75) and Tmax (2.45 ± 3.83) of BPL released from commercial brands. Moreover the attainment of greater bioavailability of BPL was most probably due to the increase in half-life (20.44 ± 2.82), mean residence time (24.81 ± 4.22) and area under the plasma concentration level curve (AUC0–24) of 9688.6 ± 4.18 for BPL released from SLMs. Convincingly, the inventive technique could not only sustain the drug release in the in vitro and in vivo environment but also maintain the plasma drug concentration level constant for a longer time without elevating Cmax.

Elements of artificial intelligence in a predictive personalized model of pharmacotherapy choice in patients with heart failure with mildly reduced ejection fraction of ischemic origin

Aim. To create and train a neural network (NN) of a predictive personalized model of pharmacotherapy choice in patients with heart failure with mildly reduced ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 170 people with HFmrEF of ischemic origin, who on the background standard pharmacotherapy, received a beta-blocker (BB) or BB+mineralocorticoid receptor antagonist eplerenone (EP): bisoprolol (BIS); BIS+EP; nebivolol (NEB); NEB+EP. Patients underwent echocardiography and were analyzed for serum aldosterone (AL), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9). To create the NN model, the following approximate predictive function of parameters was used: age, AL, TNF-α, MMP-9, sphericity index (SI), type of pharmacotherapy. The result of this function is a parameter vector: AL, TNF-α, MMP-9, SI and quality of life (QOL). The designed NN model is implemented in the Matlab software package for solving machine learning and Data Science problems. The NN model is represented as a connected graph and NN function. Dichotomous analysis was used to compare the effect of treatment types in pairs. For intergroup comparison of therapy, the Wilcoxon W test method. The critical significance (p) was considered <0,05.Results. As a result of model inference, the predicted clinical parameters of patients were obtained, depending on the influence of pharmacotherapy type on the levels of AL, TNF-α, MMP-9, and SI. Function approximation of the distribution was constructed. Determination coefficient R2 of approximating functions was ≥0,92. The calculated values for the BIS therapy groups were obtained; BIS+EP — 169,59, 82,30, 15,26 and 52,92; NEB — 186,42, 87,65, 16,10 and 57,22; NEB+EP — 171,17, 71,90, 14,22 and 58,68, respectively. There were following mean values in the vector of initial states (before therapy): AL, MMP-9, TNF-α, and QOL — 205,84, 174,16, 18,32, and 50,71, respectively. The greatest negative changes of AL, MMP-9, TNF-α (p<0,05) was observed in the NEP+EP group.Conclusion. In the course of the study, using artificial intelligence, a predictive model of a personalized approach to pharmacotherapy choice in patients with HFmrEF of ischemic origin was developed and trained. It has been established that NEP+EP therapy has the greatest effect.

A Sensitive Liquid Chromatography-Mass Spectrometric Method for Determination of Bisoprolol in Rat Serum after Pre-Column Derivatization.

Two derivatization regents were reacted with bisoprolol (BIS), followed by liquid-chromatography-mass spectrometric analysis. 3-Bromomethyl-propyphenazone (BMP) and dansyl-chloride (Dns-Cl) were reacted via the secondary amino group using a catalyst to accelerate the reaction progress and completeness with minimal reaction byproducts. The sensitivity and the ionization efficiency of both BIS-methyl-propyphenazone (BIS-MP) and BIS-Dns via electrospray ionization were studied. The sensitivity of BIS-MP was superior to BIS-Dns. The derivatization procedure, extraction procedure, and LC-MS method were optimized and validated to achieve the monitoring of BIS in rat serum at a picogram scale. The calibration curve showed a regression coefficient value of 0.999 within a concentration spanning a range of 10-500pg/mL. The detection limit and quantitation were 4 and 10pg/mL, respectively. The intraday and inter-day precision values (% relative standard deviation) ranged from 0.53 to 6.91%, whereas the accuracy values (expressed as % error) ranged from -4.20 to -0.77%. The pharmacokinetic parameters were: 15,280pg/mL for a maximum concentration of BIS (Cmax) at the maximum time (Tmax) of 1 h. BIS's elimination half-life (t1/2) was determined to be 3 h. The value of the area under the concentration-time curve (AUC0 - t) was 34,370pg/mLh.

In vitro drug-drug interaction study between Ranitidine Hydrochloride and Bisoprolol fumarate

In vitro drug-drug interaction study between Ranitidine Hydrochloride and Bisoprolol fumarate

Spectrofluorimetric determination of beta-blockers atenolol and bisoprolol fumarate residues in Senegal natural waters

A spectrofluorimetric method was developed to determine residues of two β-blockers, atenolol (AT) and bisoprolol fumarate (BF), in Senegal's natural waters. The electronic absorption and fluorescence spectral properties of both β-blockers were investigated in several organic solvent mixtures [e.g., MeOH/H2O (60/40 v/v), cyclodextrins (β-cyclodextrin, HP-β-CD], and in the presence of surfactants (SDS, Triton X, Tween 80). After optimization, satisfactory analytical figures of merit were obtained for the determination of both β-blockers: concentration linear dynamic range of over one to two orders of magnitude, limits of detection (LODs) from 1.3 to 5.4 ng/ml for BF and from 1.2 to 3.7 ng/ml for AT, limits of quantification (LOQs) from 4.5 to 18.1 ng/ml for BF and from 4.0 to 12.5 ng/ml for AT. Relative standard deviations (RSDs) were between 2.1 and 5.3 %, according to the β-blockers. The spectrofluorimetric method was applied to the analysis of fortified river water and wastewater (effluent) collected in Senegal and France and spiked with both β-blockers. It yielded good recovery values, from 93.3 to 107.8 % for AT and from 97.4 to 108.9 % for BF. Our results demonstrated the simplicity, rapidity, and sensitivity of the spectrofluorimetric method to quantify residues of β-blockers in environmental waters.