Category: 72509-76-3

Mao, Junjun published the artcileIncorporating nonlinear kinetics to improve predictive performance of population pharmacokinetic models for ciclosporin in adult renal transplant recipients: A comparison of modelling strategies, COA of Formula: C18H19Cl2NO4, the main research area is ciclosporin renoprotectant pharmacokinetic renal transplantation; Ciclosporin; Modelling strategies; Nonlinear kinetics; Population pharmacokinetics.

Ciclosporin has been shown to follow nonlinear pharmacokinetics (PK) in renal transplant recipients who received ciclosporin (Neoral, Novartis)-based triple immunosuppressive therapy. Some of these nonlinear properties have not been fully considered in population PK (popPK) anal. Therefore, the aim of this study was to determine the potential influence of nonlinearity and the functional forms of covariates on model predictability as well as to analyze multiple nonlinear factors in the in vivo process. A total of 2969 ciclosporin whole-blood measurements, including 1328 pre-dose and 1641 2-h post-dose concentrations, were collected from 173 patients who underwent their first renal transplantation. Four popPK models based on different modeling strategies were developed to investigate the discrepancy between empirical and theory-based, linear and nonlinear compartmental kinetic models and empirical formulas on model predictability. Prediction and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine the stability and predictive performance of these four models. Model predictability improved when nonlinearity was considered. The theory-based nonlinear model which incorporated nonlinear property based on known theor. relationships performed better than the other two compartmental models. The nonlinear Michaelis-Menten model showed a remarkable improvement in predictive performance compared to the other three compartmental models. The saturated binding of ciclosporin to erythrocytes, auto-inhibition induced by the inhibitory effects of ciclosporin on cytochrome P 450 3A4/P-glycoprotein may have contributed to the nonlinearity. Ciclosporin-prednisolone drug interaction should be given serious consideration in clin. settings. Incorporation of nonlinear properties is likely to be a promising approach for improving ciclosporin model predictability. Theory-based modeling is helpful to improve model predictability. However, ciclosporin nonlinear kinetics resources need further investigation.

European Journal of Pharmaceutical Sciences published new progress about Adult, mammalian. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lee, Fei Yee published the artcileAdverse drug reactions of antihypertensives and CYP3A5*3 polymorphism among chronic kidney disease patients, Computed Properties of 72509-76-3, the main research area is cytochrome polymorphism chronic kidney disease human antihypertensive drug reaction; CYP3A5; adverse drug reaction; antihypertensive drugs; chronic kidney disease; pharmacogenetics.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiol. state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

Frontiers in Pharmacology published new progress about Allele frequency. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Computed Properties of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Wanyi published the artcileEfficacy of felodipine and enalapril in the treatment of essential hypertension with coronary artery disease and the effect on levels of Salusin-β, Apelin, and PON1 gene expression in patients., Computed Properties of 72509-76-3, the main research area is .

This study aimed to analyze the effect of felodipine combined with enalapril in the treatment of patients with essential hypertension and coronary artery disease. Also, the effect of these medicines was evaluated on the peripheral blood Salusin-β, Apelin levels, and PON1 gene expression. For this purpose, 110 patients with essential hypertension combined with coronary heart disease, admitted to the hospital from January 2019 to January 2021, were selected and randomly divided into two groups. The control group was given felodipine treatment alone, and the study group was treated with combined application of felodipine and enalapril. The treatment effect, peripheral blood Salusin-β, Apelin, PON1 gene expression, and the safety of medication were compared between the two groups. The results showed that the post-treatment systolic blood pressure in the study group was 119.77 ± 5.23 mm Hg and diastolic blood pressure was 86.84 ± 5.42 mm Hg, both of which were significantly lower than those in the control group (127.81 ± 6.92 mm Hg and 95.13 ± 6.08 mm Hg), with statistically significant differences (p<0.05). The effective rates of the study group and the control group were 92.73% and 74.54% respectively, with statistically significant differences (P<0.05). The post-treatment peripheral blood Salusin-βlevel in the study group was 3.77±0.53mmol/L, and Apelin was 1.94±0.58μg/L, with statistically significant differences compared to the control group (P<0.05). The PON1 gene expression in the study group was higher than those in the control group after treatment (P<0.05). Also, the results showed that there was no statistical difference in adverse reactions between the two groups (P>0.05). According to these results, the combination of felodipine and enalapril in patients with essential hypertension combined with coronary artery disease can effectively lower the patients’ blood pressure and improve their peripheral blood Salusin-β, Apelin levels, and PON1 gene expression, thus enhancing the patients’ therapeutic effect with few adverse effects and high safety.

Cellular and molecular biology (Noisy-le-Grand, France) published new progress in MEDLINE about 72509-76-3, 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Computed Properties of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Javed, Arslan published the artcileDevelopment of Simple Dissolution Methods for Felodipine and Combined Amlodipine Besylate-Indapamide Extended Release Tablets without Stationary (Felodipine) Basket., Synthetic Route of 72509-76-3, the main research area is Felodipine basket; amlodipine besylate; dissolution; felodipine; indapamide; similarity factor; stationary hanging basket.

BACKGROUND: The dissolution method for certain drugs needs specialized conditions. Dissolution testing for felodipine extended release (ER) tablets (Plendil® 5 mg) and amlodipine-indapamide fixed dose (Natrilam®, 5/1.5 mg) ER tablets requires the use of a stationary (felodipine) basket in USP Apparatus II. OBJECTIVE: The study aimed to develop simple methods for Plendil® and Natrilam® without the use of a felodipine basket. METHODS: The dissolution profiles obtained from different media and paddle speeds were used to compute miscellaneous dissolution parameters and were compared to those obtained from standard (existing) methods using a felodipine basket. RESULTS: The f1, f2, and bootstrap f2 (5th % percentile) values for Plendil® 2.47, 88.17, and 54.62, respectively, and all other dissolution factors revealed similarity between standard and the selected test method with 1% Tween 20 at 50 rpm. For Natrilam®, f1 and f2 and bootstrap f2 5.13, 72.92, and 62.67, respectively, and all other dissolution parameters showed similarity of the standard and selected test method using 0.1N HCl media having 0.38 gm/L EDTA with a sinker at 100 rpm. Release of products assumed zero-order and Weibull model, respectively. CONCLUSION: Test dissolution methods for Plendil® and Natrilam® tablets produced equivalent dissolution profiles compared to their respective standard methods with stationary basket USP Apparatus II.

Current pharmaceutical design published new progress about Felodipine basket; amlodipine besylate; dissolution; felodipine; indapamide; similarity factor; stationary hanging basket. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Synthetic Route of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Maurya, Priyanka published the artcileAppraisal of Felodipine Nanocrystals for Solubility Enhancement and Pharmacodynamic Parameters on Cadmium Chloride Induced Hypertension in Rats., Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Antisolvent precipitation; cadmium chloride; crystallinity; felodipine; heart rate variability; heat of fusion.

AIM: Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the Nanocrystal (NC) approach. METHODS: FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation. RESULTS: Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content. CONCLUSION: The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensure that FDP-NC can be safely stored at 25°C. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP.

Current drug delivery published new progress about Antisolvent precipitation; cadmium chloride; crystallinity; felodipine; heart rate variability; heat of fusion. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chretien, Marc L published the artcileSeverity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study., Related Products of pyridine-derivatives, the main research area is adverse events; clinical pharmacology; coeliac disease; gastroenterology.

OBJECTIVE: Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study. SETTING: London, Ontario, Canada. PARTICIPANTS: Patients with coeliac disease (n=47) with positive serology and healthy individuals (n=68). MAIN OUTCOME MEASURES: Patients with coeliac disease-upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals-oral felodipine pharmacokinetics study with water and grapefruit juice. RESULTS: Coeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0-8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0-8 (11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice. CONCLUSIONS: Increased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity. BMJ open published new progress about adverse events; clinical pharmacology; coeliac disease; gastroenterology. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Liu, Lei published the artcileWater-Resistant Drug-Polymer Interaction Contributes to the Formation of Nano-Species during the Dissolution of Felodipine Amorphous Solid Dispersions, Synthetic Route of 72509-76-3, the main research area is amorphous solid dispersion; drug−polymer interaction; intrinsic dissolution; nano-species; water resistant.

Drug-polymer interactions are of great importance in amorphous solid dispersion (ASD) formulation for both dissolution performance and phys. stability considerations. In this work, three felodipine ASD systems with drug loading ranging from 5 to 20% were prepared using PVP, PVP-VA, or HPMC-AS as the polymer matrix. The amorphization and homogeneity were confirmed by differential scanning calorimetry and powder X-ray diffraction. The intrinsic dissolution behavior of these ASDs was studied in 0.05 M HCl and phosphate-buffered saline (PBS) (pH 6.5). In 0.05 M HCl, PVP-VA ASDs with low drug loading (<15%) showed rapid dissolution accompanied with nano-species generation, while in the PVP system, rapid dissolution and nano-species generation were observed only when drug loading was less than 10%, and HPMC-AS ASDs always released slowly with no nano-species formation. In PBS, PVP-VA ASDs with drug loading less than 10% showed rapid dissolution accompanied with nano-species generation, while for PVP ASDs, rapid dissolution and nano-species generation were observed only when drug loading was 5%. However, 20% drug loading HPMC-AS ASDs exhibited rapid dissolution of felodipine and nano-species generation. When the drug loading was above the transition point of PVP-VA ASDs and PVP ASDs, the release rate was significantly lowered, and no nano-species was generated. To understand this phenomenon, drug-polymer interactions were studied using the m.p. depression method and the Flory-Huggins model fitting. The Flory-Huggins interaction parameters (χ) for felodipine/HPMC-AS, felodipine/PVP, and felodipine/PVP-VA were determined to be 0.62 ± 0.07, -0.55 ± 0.20, and -1.02 ± 0.21, resp., indicating the existence of the strongest attractive mol. interaction between felodipine and PVP-VA, followed by felodipine/PVP, but not in felodipine/HPMC-AS. Furthermore, dynamic vapor sorption further revealed that the mol. interactions between felodipine and PVP or PVP-VA were resistant to water. We concluded that water-resistant drug-polymer interactions in felodipine/polymer systems were responsible for the formation of nano-species, which further facilitated the rapid initial drug dissolution Molecular Pharmaceutics published new progress about amorphous solid dispersion; drug−polymer interaction; intrinsic dissolution; nano-species; water resistant. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Synthetic Route of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Poozesh, Sadegh published the artcileMulticomponent Droplet Drying Modeling Based on Conservation and Population Balance Equations, COA of Formula: C18H19Cl2NO4, the main research area is amorphous solid dispersion; drying kinetics; mathematical modeling; multicomponent droplet; particle engineering.

Abstract: The aim of this work is to present a modeling tool to describe drying kinetics and delineate evolving phys. and chem. behavior of multicomponent droplets during drying. Conservation equations coupled with population balance equations (PBE) are used to achieve this goal. Modeling results are gauged with single salt-water droplet drying from literature and show congruent trends. This model is then extended to a more complex system: various droplet sizes containing methanol (solvent), Felodipine (active ingredient), and PVP (polyvinylpyrrolidone as excipient). The FIB-SEM (Focused-Ion Beam SEM) imaging results from spray-dried particles produced with similar formulation and processing conditions are consistent with phase behavior predicted by the model. The results show competing impacts of transport phenomena on the intermittent shell formation process and final particle structure and chem. heterogeneity. Solute diffusion, solvent efflux, and intra-drop flow impact the model system. It is found that shell formation follows a fluctuating profile where the initial precipitation of the dissolved species on the droplet surface is dampened, and nucleated particles become dispersed periodically until the shell becomes strong enough to withstand internal circulations. These internal effects are dependent on droplet size and are pronounced for larger droplets. That is, the particle phase behavior and phys. nature are functions of the atomized droplet size. Stemming understating from this study would inform an optimized unit, operating in target design space. This would provide better product quality control and minimize discrepancies observed in process development during the early phase vs. com. scale.

Pharmaceutical Research published new progress about amorphous solid dispersion; drying kinetics; mathematical modeling; multicomponent droplet; particle engineering. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tingle, Samuel J. published the artcileCalcium channel blockers in pancreatic cancer: increased overall survival in a retrospective cohort study, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is pancreatic cancer hypertension Iercanidipine amlodipine calcium channel blocker.

This retrospective cohort study aimed to translate this into the clinic by investigating the effect of CCBs on survival in pancreatic cancer. One hundred sixty-four patients with unresectable pancreatic ductal adenocarcinoma were included. Data were collected on CCB prescription, and for a range of other potentially important prognostic factors: ECOG performance status, AJCC cancer stage, chemotherapy regimen, radiotherapy, age, hypertension and sex. Participants prescribed CCB (n = 30) were more likely to be older (P = 0.004) and have hypertension (P < 0.0005); baseline demographics were otherwise similar between groups. On adjusted cox regression patients prescribed CCBs demonstrated significantly improved overall survival; hazard ratio -0.496 (0.297-0.827; P = 0.007). Performance status (P < 0.0005), tumor stage (P < 0.0005), chemotherapy regimen (P < 0.0005), radiotherapy (0.002) and age (P = 0.012) were also independent predictors of survival. The Kaplan-Meier estimated median survival was 15.3 mo for patients prescribed CCBs vs. 10.1 mo for patients not prescribed CCBs (P = 0.131). This study supports previous work suggesting CCBs may be beneficial in pancreatic cancer. Further work on larger datasets will allow for subgroup anal. delineating the effects of specific CCBs in combination with different forms of chemotherapy, paving the way for future prospective studies. Anti-Cancer Drugs published new progress about Biopsy. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tepech-Carrillo, Carlos published the artcileStudy of the reactivity of (100) felodipine surface model based on DFT concepts, Formula: C18H19Cl2NO4, the main research area is felodipine reactivity density functional theory surface model.

In this study, D. Functional Theory including a dispersion correction is employed to model and analyze the structural, electronic and local reactivity of the (100) surface of felodipine. The surface energy calculated at the Generalized Gradient Approximation (GGA) level, along with plane waves as basis set and ultrasoft pseudopotentials, shows that the (100) surface is the most stable as compared to the (010) and (110) ones. In particular, we have focused on performing a quant. study of the reactivity of the surface by means of the Fukui function and through the HOMO and LUMO populations. Our results can be related to some applications in the pharmaceutical chem. of this compound

Open Journal of Physical Chemistry published new progress about Atoms. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem