Month: December 2022

Poulin, Patrick published the artcileApplication of the Tissue Composition-Based Model to Minipig for Predicting the Volume of Distribution at Steady State and Dermis-to-Plasma Partition Coefficients of Drugs Used in the Physiologically Based Pharmacokinetics Model in Dermatology, Computed Properties of 72509-76-3, the main research area is dermis partition drug pharmacokinetics model dermatol; IVIVE; PBPK modeling; discovery; in silico; pharmacokinetics; tissue composition; topical; transdermal.

The minipig continues to build a reputation as a viable alternative large animal model to predict humans in dermatol. and toxicol. studies. Therefore, it is essential to describe and predict the pharmacokinetics in that species to speed up the clin. candidate selection. Essential input parameters in whole-body physiol. based pharmacokinetic models are the tissue-to-plasma partition coefficients and the resulting volume of distribution at steady-state (Vss). Mechanistic in vitro- and in silico-based models used for predicting these parameters of tissue distribution of drugs refer to the tissue composition-based model (TCM). Robust TCMs were initially developed for some preclin. species (e.g., rat and dog) and human; however, there is currently no model available for the minipig. Therefore, the objective of this present study was to develop a TCM for the minipig and to estimate the corresponding tissue composition data. Drug partitioning into the tissues was predominantly governed by lipid and protein binding effects in addition to drug solubilization and pH gradient effects in the aqueous phase on both sides of the biol. membranes; however, some more complex tissue distribution processes such as drug binding to the collagen-laminin material in dermis and a restricted drug partitioning into membranes of tissues for compounds that are amphiphilic and contain sulfur atom(s) were also challenged. The model was validated by predicting Vss and the dermis-to-plasma partition coefficients (Kp-dermis) of 68 drugs. The prediction of Kp-dermis was extended to humans for comparison with the minipig. The results indicate that the extended TCM provided generally good agreements with observations in the minipig showing that it is also applicable to this preclin. species. In general, up to 86% and 100% of the predicted Vss values are resp. within 2-fold and 3-fold errors compared to the exptl. determined values, whereas these numbers are 78% and 94% for Kp-dermis when the anticipated outlier compounds are not included. Binding data to dermis are comparable between minipigs and humans. Overall, this study is a first step toward developing a mechanistic TCM for the minipig, with the aim of increasing the use of physiol. based pharmacokinetic models of drugs for that species in addition to rats, dogs, and humans because such models are used in preclin. and clin. transdermal studies.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Blood plasma. 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

Carling, Carl-Johan published the artcileMilling of poorly soluble crystalline drug compounds to generate appropriate particle sizes for inhaled sustained drug delivery, Quality Control of 72509-76-3, the main research area is lung inhaled sustained drug delivery; particle size AZD4854 milling dissolution; Dissolution; Inhaled sustained drug delivery; Milling; Nebulization; Suspension; Ultrasound.

One of the simplest design concepts of inhaled sustained drug delivery to the lung is to utilize the slow dissolution of drug crystals with poor aqueous solubility An optimum dissolution rate, and thereby a delivery profile locally in the lung tissue, can be achieved in a reliable way by selecting a compound with an appropriate combination of solubility and particle size. It is in our experience relatively straightforward to manufacture monomodal particle size distributions of poorly soluble drug crystals in the mass median diameter range of either a few micrometers or a few hundred nanometers, but very challenging to manufacture a monomodal distribution in the range intermediate to these two. In this manuscript, we describe an investigation with the objective of generating desired particle sizes in the whole size range from a few micrometers to a few hundred nanometers for inhaled sustained drug delivery, by utilizing Adaptive Focused Acoustic (AFA) milling and planetary bead-milling. By combining the two different milling techniques it was possible to produce two to three distinctly different monomodal or almost monomodal particle size distributions in the desired particle size range of each of the model drug compounds in milligram scale. The dissolution kinetics of the different particle sizes of the model drugs were measured exptl. as well as predicted theor., showcasing that the dissolution kinetics can be characterized, predicted and significantly changed in a controlled way by modifying the particle size. For one of the model drugs, it was shown in an in vivo rat study that the inhaled sustained drug delivery profile in the lung tissue could be significantly changed by modifying the particle size of the drug.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Blood plasma. 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, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Iwasaki, Shinji published the artcileApplication of unbound liver-to-plasma concentration ratio to quantitative projection of cytochrome P450-mediated drug-drug interactions using physiologically based pharmacokinetic modelling approach, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is liver plasma cytochrome drug interaction PBPK modeling approach; Drug–drug interaction; K; human cryopreserved hepatocytes; physiologically based pharmacokinetic model.

1. This study evaluated the prediction accuracy of cytochrome P 450 (CYP)-mediated drug-drug interaction (DDI) using minimal physiol.-based pharmacokinetic (PBPK) modeling incorporating the hepatic accumulation factor of an inhibitor (i.e. unbound liver/unbound plasma concentration ratio [Kp,uu,liver]) based on 22 clin. DDI studies.2. Kp,uu,liver values were estimated using three methods: (1) ratio of cell-to-medium ratio in human cryopreserved hepatocytes (C/Mu) at 37°C to that on ice (Kp,uu,C/M), (2) multiplication of total liver/unbound plasma concentration ratio (Kp,u,liver) estimated from C/Mu at 37°C with unbound fraction in human liver homogenate (Kp,uu,cell) and (3) observed Kp,uu,liver in rats after i.v. infusion (Kp,uu,rat).3. PBPK model using each Kp,uu,liver projected the area under the curve (AUC) increase of substrates more accurately than the model assuming a Kp,uu,liver of 1 for the average fold error and root mean square error did. Particularly, the model with a Kp,uu,liver of 1 underestimated the AUC increase of triazolam following co-administration with CYP3A4 inhibitor itraconazole by five-fold, whereas the AUC increase projected using the model incorporating the Kp,uu,C/M, Kp,uu,cell, or Kp,uu,rat of itraconazole and hydroxyitraconazole was within approx. two-fold of the actual value.4.

Xenobiotica published new progress about Blood plasma. 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

Possomato-Vieira, Jose Sergio published the artcileCirculating levels of hydrogen sulphide negatively correlate to nitrite levels in gestational hypertensive and preeclamptic pregnant women, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is gestational hypertensive hydrogen sulfide neg correlate pregnant women; gestational hypertension; hydrogen sulphide; nitrite; preeclampsia; pregnancy.

Endothelial dysfunction is a hallmark of preeclampsia and the role of nitric oxide (NO) has been extensively studied in this pregnancy complication. In recent years, hydrogen sulfide (H2S) has arisen as a new gasotransmitter with an impact on endothelial function. However, the involvement of H2S in the pathophysiol. of preeclampsia is not fully understood, and only a few studies with limited sample size have investigated circulating levels of H2S in preeclamptic patients. Moreover, H2S levels have not been previously evaluated in gestational hypertension. Furthermore, the relationship between H2S and NO in these hypertensive disorders of pregnancy has yet to be determined We measured H2S levels in plasma of 120 healthy pregnant women, 88 gestational hypertensive and 62 preeclamptic women. We also measured plasma nitrite in a subset of patients and carried out correlation anal. between plasma H2S and nitrite in these three groups. We found that plasma H2S was elevated in preeclampsia and further increased in gestational hypertension compared to healthy pregnancy. Plasma nitrite was reduced in gestational hypertension and preeclampsia, and these levels were neg. correlated with H2S in both gestational hypertension and preeclampsia, but not in healthy pregnancy. Our results indicate that increases in H2S may represent a mechanism triggered as an attempt to compensate reduced NO in gestational hypertension and preeclampsia. Future studies are warranted to investigate the mechanisms underlying H2S/NO interaction on mediating endothelial dysfunction in these hypertensive disorders of pregnancy.

Clinical and Experimental Pharmacology and Physiology published new progress about Blood plasma. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Salunkhe, N. H. published the artcileValidated RP-HPLC method for quantification of felodipine in rabbit plasma: Application in a bioequivalence study, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is RP HPLC method felodipine rabbit plasma; Felodipine; La nimodipine; Nimodipine; Plasma de lapin; RP-HPLC; Rabbit plasma; Validation.

The aim of present study was to develop a simple, rapid, selective, sensitive and robust reverse phase high performance liquid chromatog. method for quantification of felodipine in rabbit plasma at the wavelength of 360 nm. Protein was precipitated from rabbit plasma sample by addition of acetonitrile as a vehicle. An isocratic elution of samples was performed on capcell pak C8 DD S5 column (4.6 mm × 250 mm particle size 5μm) column with mobile phase consisting 5 mM Phosphate Buffer (pH 4.8 adjusted with dilute ortho-phosphoric acid solution): acetonitrile (25:75:volume/volume) delivered at flow rate 1.0 mL min-1. A good linear response was achieved over the range of 0.25-20.00 g mL-1. LODs and LOQs for felodipine were found to be 0.055 and 0.201μg mL-1, resp. The method was quant. evaluated in terms of linearity, precision, accuracy (recovery), selectivity robustness and stability study as per standard guidelines. The validated RP-HPLC method was successfully applied for the bioavailability studies of felodipine. The pharmacokinetic parameters were calculated for all the investigated drugs in rabbit after single-dose administrations of pure drug and formulation of felodipine. Finally, the obtained results for the application of the proposed RP-HPLC method proved its efficiency to be applied to the therapeutic drug monitoring (TDM) and bioequivalence (BE) studies. Thus, developed method is simple, convenient and suitable for the anal. of felodipine in bulk and pharmaceutical formulations.

Annales Pharmaceutiques Francaises published new progress about Blood plasma. 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

Parker, John D. published the artcileComparison of short-acting versus extended-release nifedipine: Effects on hemodynamics and sympathetic activity in patients with stable coronary artery disease, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is coronary artery disease sympathetic activity hemodynamics nifedipine.

Abstract: We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodol. in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7-10 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6 h. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30 min) and was much greater than that observed in the extended release group, which occurred later (270 min). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.

Scientific Reports published new progress about Blood plasma. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Maher, M. A. published the artcileNifedipine alone or combined with sildenafil citrate for management of threatened preterm labour: a randomised trial, Category: pyridine-derivatives, the main research area is nifedipine sildenafil citrate human preterm labor; Nifedipine; prematurity; sildenafil citrate; threatened preterm labour; tocolytic therapy.

To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL). Prospective randomised study. An Egyptian university hospital. Women with threatened PTL who received either nifedipine with SC or nifedipine alone. Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6-8 h at the same time as vaginal administration of SC (25 mg at 8-hourly intervals) or (2) nifedipine alone. Medications were continued for 48-72 h. The percentage of women who remained undelivered during hospitalisation. From Jan. 2015 to Nov. 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 vs. 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 vs. 20.3%; P = 0.014), prolonged latency (29 vs. 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 vs. 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to <32 wk, 20.7 vs. 38.1%; P = 0.043), and increased neonatal birthweight (1900 vs. 1500 g; P = 0.018). Vaginal SC combined with nifedipine is an effective option for tocolytic therapy during threatened PTL. Vaginal SC enhances the tocolytic effect of nifedipine. BJOG published new progress about Birth weight. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Suslu, Incilay published the artcileElectrochemical detection of antioxidant activities of 4-indolyl-5-oxo-6,6 (or 7,7) -dimethyl-1,4,5,6,7,8-hexahydroquinoline derivatives, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is hexahydroquinoline derivative nifedipine antioxidant activity differential pulse voltammetry.

Antioxidants used in different medical and industrial fields in order to prevent and delay oxidative stress. They play a crucial role in the protecting biol. systems against many diseases. 1,4-dihydropyridines are known as calcium channel modulators. Electrochem. techniques are simple, cheap and fast detection techniques and require small amounts of sample, so they offer advantages over commonly used anal. methods. Voltammetric methods have been applied to investigated the antioxidant activity of compounds in different fields. The proposed work is aimed at examining the electrochem. behavior of the 1,4-dihydropyridines by differential pulse voltammetry and hence the assessment of its antioxidant activity from the cathodic reduction peak of oxygen values. The peak current due to oxygen reduction was found to be proportional to the 1,4-dihydropyridines concentration of 0.1 – 0.5 mg/mL. The coefficient of antioxidant activity of 1,4-dihydropyridine derivatives were calculated and compared each other. Nifedipine used as a reference drug that is known as the calcium channel modulator and it is used to compare the antioxidant activities of 1,4-dihydropyridine-derived compounds

Journal of Research in Pharmacy published new progress about Antioxidants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ferreira, Paula Benvindo published the artcileSupplementation with Spirulina platensis Prevents Uterine Diseases Related to Muscle Reactivity and Oxidative Stress in Rats Undergoing Strength Training, Category: pyridine-derivatives, the main research area is Spirulina supplementation muscle oxidative stress uterine disease; Spirulina platensis; muscle reactivity; oxidative stress; physical exercise; uterus.

Strength training increases systemic oxygen consumption, causing the excessive generation of reactive oxygen species, which in turn, provokes oxidative stress reactions and cellular processes that induce uterine contraction. The aim of this study was to evaluate the possible protective effect of Spirulina platensis (SP), an antioxidant blue algae, on the contractile and relaxation reactivity of rat uterus and the balance of oxidative stress/antioxidant defenses. Female Wistar rats were divided into sedentary (CG), trained (TG), and T + supplemented (TG50, TG100) groups. Reactivity was analyzed by AQCAD, oxidative stress was evaluated by the malondialdehyde (MDA) formation, and the antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Strength training increased contractile reactivity and decreased the pharmaco-mech. component of relaxing reactivity in rat uterus. In addition, training decreased oxidation inhibition in the plasma and exercise increased oxidative stress in the uterine tissue; however, supplementation with algae prevented this effect and potentiated the increase in antioxidant capacity. Therefore, this study demonstrated that food supplementation prevents changes in reactivity and oxidative stress induced by strength training in a rat uterus, showing for the first time, that the uterus is a target for this exercise modality and antioxidant supplementation with S. platensis is an alternative means of preventing uterine dysfunction.

Nutrients published new progress about Antioxidants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Viana-Mattioli, Sarah published the artcileSIRT1-dependent effects of resveratrol and grape juice in an in vitro model of preeclampsia, Synthetic Route of 21829-25-4, the main research area is preeclampsia resveratrol and grape juice sirtuin effect; Endothelium; Grape juice; Nitric oxide; Oxidative stress; Preeclampsia; Resveratrol; SIRT1.

Preeclampsia (PE) is a multifactorial hypertensive disorder of pregnancy that is partly responsible for both maternal and fetal morbidity and mortality levels worldwide. It has been recently discovered that sirtuin-1 (SIRT1) is reduced in the circulation and in an in vitro model of PE. Therefore, in this study, we investigated the effects of trans-resveratrol, a potent antioxidant and activator of SIRT1, on oxidative stress and nitric oxide (NO) production in an in vitro model of PE compared to gestational hypertensive (GH) and healthy pregnant (HP) women. Furthermore, we also evaluated the effects of an acute intake of grape juice on women with PE to assess whether it could mimic in vitro trans-resveratrol supplementation. (1) In the GH group, resveratrol decreased intracellular reactive oxygen species (ROS) and increased their antioxidant capacity, while inhibiting SIRT1 reestablished previous levels. (2) In PE, inhibition of SIRT1 increased antioxidant activity. (3) Intracellular NO and supernatant nitrite levels were increased by inhibiting SIRT1 in the PE group. (4) Grape juice intake increased intracellular NO levels vs. before grape juice intake control; however, the inhibition of SIRT1 before grape juice intake initially increased NO, but decreased it 1 h after grape juice intake. In conclusion, activating SIRT1 by using resveratrol alone may not be beneficial to women with PE, and GH and PE seem to have different responsive mechanisms to this mol. Furthermore, grape juice intake seems to have different effects compared to resveratrol supplementation alone in this in vitro model of PE, demonstrating the potential of the combination of other biol. active mols. from grape juice over the SIRT1-eNOS-NO in PE treatment.

Biomedicine & Pharmacotherapy published new progress about Antioxidants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem