Tag: M.W=200-350

Zhu, Yun-Ting published the artcileEffects of apatinib on the pharmacokinetics ofnifedipine and warfarin in patients with advancedsolid tumors, Formula: C17H18N2O6, the main research area is CYP2C9; CYP3A4; apatinib; drug-drug interaction; nifedipine; warfarin.

Background and Purpose: Apatinib is a small-mol. tyrosine kinase inhibitor for the treatment of recurrent or progressive advanced-stage gastric adenocarcinoma or gastroesophageal junction cancer. The in vitro inhibition studies suggested that apatinib exerted potent inhibition on CYP3A4 and CYP2C9. To evaluate the potential of apatinib as a perpetrator in CYP450-based drug-drug interactions in vivo, nifedipine and warfarin were, resp., selected in the present study as the probe substrates of CYP3A4 and CYP2C9 for clin. drug-drug interaction studies. Since hypertension and thrombus are common adverse effects of vascular targeting anticancer agents, nifedipine and warfarin are usually coadministered with apatinib in clin. practice. Methods: A single-center, open-label, single-arm, and self-controlled trial was conducted in patients with advanced solid tumors. The patients received a single dose of 30 mg nifedipine on Day 1/14 and a single dose of 3 mg warfarin on Day 3/16. On Day 9-21, the subjects received a daily dose of 750 mg apatinib, resp. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, resp., investigated. Results: Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC0-48h and Cmax of nifedipine by 83% (90% confidence interval [CI] 1.46-2.31) and 64% (90% CI 1.34-2.01), resp. Similarly, coadministration with apatinib contributed to the significant increases of AUC0-t and Cmax of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), resp. Conclusion: Concomitant apatinib administration resulted in significant increases in systemic exposure to nifedipine and S-warfarin. Owing to the risk of pharmacokinetic drug-drug interactions based on CYP3A4/CYP2C9 inhibition by apatinib, caution is advised in the concurrent use of apatinib with either CYP2C9 or CYP3A4 substrates.

Drug Design, Development and Therapy published new progress about CYP2C9; CYP3A4; apatinib; drug-drug interaction; nifedipine; warfarin. 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, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Fu, Chengxiao published the artcilePopulation Pharmacokinetic Modelling for Nifedipine to Evaluate the Effect of Parathyroid Hormone on CYP3A in Patients with Chronic Kidney Disease., Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is CYP3A; chronic kidney disease; nifedipine; parathyroid hormone; population pharmacokinetic.

Purpose: Parathyroid hormone (PTH) can induce the downregulation of CYP3A in chronic kidney disease (CKD). Nevertheless, the effect of PTH on CYP3A-mediated clearance pathways from a clinical perspective remains unclear. Methods: This study employed population pharmacokinetic (PopPK) modeling to delineate potential changes in CYP3A activity in patients with CKD. Pharmacokinetic data for nifedipine, a typical CYP3A substrate, as well as covariate information, were prospectively collected from 157 patients with a total of 612 concentrations. PopPK data analysis was performed using a nonlinear mixed-effects model. Results: The pharmacokinetics of nifedipine were optimally described according to a one-compartment model with zero-order absorption and first-order elimination. The estimated population parameters (and interindividual variability) were apparent clearance (CL/F) 49.61 L/h (58.33%) and apparent volume of distribution (V/F) 2300.26 L (45.62%), and the PTH level negatively correlated with CL/F. In comparison with the reference level, it was observed that the dosage of nifedipine should be reduced with the maximum boundary value of PTH, after a Monte Carlo simulation. Conclusion: This study provides insight into the effects of PTH on CYP3A-mediated clearance pathways. Moreover, PTH could be used as a guide for the appropriate administration of CYP3A eliminated drugs in patients with CKD.

Drug design, development and therapy published new progress about CYP3A; chronic kidney disease; nifedipine; parathyroid hormone; population pharmacokinetic. 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, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Morikawa, Satoru published the artcileTreatment of calcium channel blocker-induced gingival overgrowth without modifying medication., Product Details of C17H18N2O6, the main research area is dentistry and oral medicine; hypertension.

Gingival overgrowth is a common side effect of calcium channel blockers used in the treatment of cardiovascular diseases. While controversial, management includes discontinuing the calcium channel blocker. We report the case of a 66-year-old Japanese man with hypertension and type 2 diabetes mellitus who was diagnosed with severe periodontitis covering almost all the teeth. The patient had been on nifedipine (40 mg/day) and amlodipine (10 mg/day) medication for 5 years. With his physician’s consent, nifedipine was discontinued during his treatment for periodontitis, which consisted of oral hygiene instructions and scaling and root planing on all areas. Gingivectomy was performed on the areas of hard fibrous swelling. Nifedipine was resumed during periodontal treatment when the patient’s hypertension worsened. His periodontal scores improved when he resumed treatment. We report that significant improvement in gingival overgrowth can occur with basic periodontal treatment, surgery and sustained intensive follow-up without adjusting calcium channel blockers.

BMJ case reports published new progress about dentistry and oral medicine; hypertension. 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, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gainder, Shalini published the artcileTo study the changes in fetal hemodynamics with intravenous labetalol or nifedipine in acute severe hypertension., Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Doppler; Hypertension; Labetalol; Nifedipine; Pregnancy.

OBJECTIVE: To compare the efficacy of intravenous labetalol or oral nifedipine in treatment of acute maternal hypertension and study the fetal hemodynamic changes using color Doppler ultrasound that follows treatment. STUDY DESIGN: Thirty women with severe preeclampsia having acute hypertension (more than or equal to 160/105 mmHg) were randomized in 2 groups to receive intravenous labetalol or oral nifedipine until blood pressure was lowered to less than or equal to 140/90 mmHg. Doppler vascular indices namely pulsatility index, resistance index, S/D ratio of umbilical (UA) and middle cerebral artery (MCA) were measured baseline at the time of acute severe hypertension and repeated after control of blood pressure, to assess the changes in fetal hemodynamics if any with labetalol or nifedipine. RESULTS: Both nifedipine and labetalol were found to be effective when used for rapid control of blood pressure. Mean age of women in both groups and mean gestational age was statistically comparable. No change in fetal heart rate before and after treatment was observed in both groups. Doppler vascular indices of UA and MCA showed no significant changes as compared to baseline values in both groups. CONCLUSION: The use of labetalol and nifedipine were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. Choice between these two drugs should be based on cost, availability respective contraindications, and clinician’s experience.

Pregnancy hypertension published new progress about Doppler; Hypertension; Labetalol; Nifedipine; Pregnancy. 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, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Doherty, Anne published the artcileHemodynamic Complications in Pregnancy: Preeclampsia and Beyond., Formula: C17H18N2O6, the main research area is Endothelial inflammation; Fetal growth restriction; Hemodynamic adaptation; Preeclampsia; Vascular remodeling.

Normal pregnancy is a complex and dynamic process that requires significant adaptation from the maternal system. Failure of this adaptive process in pregnancy contributes to many pregnancy related disorders, including the hypertensive disorders of pregnancy. This article discusses placental development and how abnormalities in the process of vascular remodeling contribute to the multisystem maternal and fetal disease that is preeclampsia and fetal growth restriction. We review some of the consequences of this condition on the mother and fetus, aspects of the clinical management of preeclampsia and how it can influence both mother and infant in the postnatal period and beyond.

Clinics in perinatology published new progress about Endothelial inflammation; Fetal growth restriction; Hemodynamic adaptation; Preeclampsia; Vascular remodeling. 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, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Alavifard, Sepand published the artcileFirst-line antihypertensive treatment for severe hypertension in pregnancy: A systematic review and network meta-analysis., Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Antihypertensive agents; Hydralazine; Labetalol; Network meta-analysis; Nifedipine; Pregnancy-induced hypertension.

BACKGROUND: Hydralazine, labetalol, and nifedipine are the recommended first-line treatments for severe hypertension in pregnancy. While all three are effective, there is a lack of sufficient evidence regarding their comparative safety and efficacy. OBJECTIVE: To determine the comparative safety and efficacy of the first-line treatment options for severe hypertension in pregnancy. METHODS: A systematic search of Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 31, 2018 was conducted. RCTs in pregnancy comparing a first-line antihypertensive agent to another first-line agent for the treatment of severe hypertension in pregnancy. Screening, data abstraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a Bayesian network meta-analysis with vague priors was conducted. MAIN RESULTS: Of the 1330 publications identified, 17 RCTs comprised of a total of 1591 women met our selection criteria. For successful treatment of severe hypertension, nifedipine was found to be superior to hydralazine (OR 4.13 [95% CrI 1.01-20.75]) but not labetalol (OR 3.43 [95% CrI 0.94-19.95]). This was not associated with an increased risk for caesarean delivery or maternal side effects. There was no significant difference between labetalol and hydralazine. CONCLUSIONS: Given the results of this systematic review and network meta-analysis, maternity care providers should feel comfortable initiating management of severe hypertension in pregnancy using oral nifedipine.

Pregnancy hypertension published new progress about Antihypertensive agents; Hydralazine; Labetalol; Network meta-analysis; Nifedipine; Pregnancy-induced hypertension. 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

Wautlet, Cynthie K published the artcileHypertensive Crisis in Pregnancy., Related Products of pyridine-derivatives, the main research area is Antihypertensive treatment; Hypertension; Hypertensive crisis; Preeclampsia; Pregnancy.

Severe hypertension in pregnancy is a medical emergency, defined as systolic blood pressure (BP) â‰?160 mm Hg and/or diastolic BP â‰?110 mm Hg taken 15 minutes to 4 or more hours apart. Outside pregnancy, acute severe hypertension (HTN) is defined as a BP greater than 180/110 to 120 reproducible on 2 occasions. The lower threshold for severe HTN in pregnancy reflects the increased risk for adverse outcomes, particularly maternal stroke and death, and may be a source of under-recognition and treatment delay, particularly in nonobstetrical health care settings. Once a severe hypertension episode is recognized, antihypertensive therapy should be initiated as soon as feasibly possible, at least within 30 to 60 minutes. Intravenous (IV) labetalol, hydralazine, and oral immediate-release nifedipine are all recommended first-line agents and should be administered according to available institutional protocols and based on provider knowledge and familiarity.

Obstetrics and gynecology clinics of North America published new progress about Antihypertensive treatment; Hypertension; Hypertensive crisis; Preeclampsia; Pregnancy. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yao, Xin published the artcileSurfactants Accelerate Crystallization of Amorphous Nifedipine by Similar Enhancement of Nucleation and Growth Independent of Hydrophilic-Lipophilic Balance, Related Products of pyridine-derivatives, the main research area is ASDs; HLB; amorphous; crystal growth; crystal nucleation; crystallization kinetics; nifedipine; nonionic surfactants.

Amorphous formulations, increasingly employed to deliver poorly soluble drugs, generally contain surfactants to improve wetting and dissolution These surfactants are often liquids and can potentially increase the mobility of the drug and reduce its stability, but little is known about this effect. Here we investigate the effect of four common nonionic surfactants (Tween 80, Span 80, Triton X-100, and Poloxamer 407) on the crystallization of amorphous nifedipine (NIF). We find that the surfactants significantly enhance the rates of crystal nucleation and growth even at low concentrations, by up to 2 orders of magnitude at 10 wt %. The surfactants tested show similar enhancement effects independent of their structural details and hydrophilic-lipophilic balance (HLB), suggesting that surfactant adsorption at solid/liquid interfaces does not play a major role in crystal nucleation and growth. Importantly, the surfactants accelerate crystal nucleation and growth by a similar factor. This result mirrors the previous finding that a polymer dopant in a mol. glass-former causes similar slowdown of nucleation and growth. These results indicate that nucleation and growth in a deeply supercooled liquid are both mobility-limited, and a dopant mainly functions as a mobility modifier (enhancer or suppressor depending on the dopant). The common surfactants tested are all mobility enhancers and destabilize the amorphous drug, and this neg. effect must be managed using stabilizers such as polymers. The effect of surfactants on nucleation can be predicted from the effect on crystal growth and the crystallization kinetics of the pure system, using the same principle previously established for drug-polymer systems. We show how the independently measured nucleation and growth rates enable predictions of the overall crystallization rates.

Molecular Pharmaceutics published new progress about ASDs; HLB; amorphous; crystal growth; crystal nucleation; crystallization kinetics; nifedipine; nonionic surfactants. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Szychowski, Konrad A. published the artcileCalcium channel antagonists interfere with the mechanism of action of elastin-derived peptide VGVAPG in mouse cortical astrocytes in vitro, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Astrocyte; Cat; Elastin-derived peptides; IL-1β; Pparγ; VGVAPG.

Elastin-derived peptides (EDPs) contain replications of the Val-Gly-Val-Ala-Pro-Gly (VGVAPG) hexapeptide. It has been described that the VGVAPG peptide induces reactive oxygen species (ROS) production in murine monocytes and astrocytes, human fibroblasts, and the human neuroblastoma (SH-SY5Y) cell line. To date, there is growing evidence that calcium channel blockers (CCBs) reduce oxidative stress and development of inflammation in the nervous system. Therefore, the aim of the present study was to evaluate the impact of such CCBs as Nifedipine, Verapamil, and MK-801 on the expression of peroxisome proliferator-activated receptor (Pparγ), i.e. ROS-related and inflammation-related proteins, in mouse astrocytes exposed in vitro to the VGVAPG peptide. The experiments showed that Nifedipine or MK-801 used in co-treatment with the VGVAPG peptide potentiated the effect of this peptide on the Pparγ level after the 24-h and 48-h treatment. Moreover, all studied compounds decreased the VGVAPG-induced caspase-1 activity in both time intervals. The data also showed that the VGVAPG peptide decreased the interleukin 1 beta (IL-1β) level in both studied time intervals. Upon a short-time exposure, the use of CCBs intensified the decrease in IL-1β stimulated by the VGVAPG peptide, opposite to the longer treatment. Moreover, the VGVAPG peptide decreased the IL-1βR1 level in both studied time intervals. After 24 h, Nifedipine and Verapamil potentiated the effect of the VGVAPG peptide. The VGVAPG peptide decreased the catalase (Cat) protein expression only after 24 h, whereas CCBs did not affect the expression of Cat induced by the VGVAPG peptide. The VGVAPG peptide increased the expression of the superoxide dismutase 1 (Sod1) protein. After 24 h of exposure, Nifedipine and Verapamil potentiated the increase in the Sod1 protein expression. Finally, our data showed that VGVAPG did not change the level of estradiol (E2) in the astrocytes. Interestingly, Nifedipine and Verapamil in co-treatment with VGVAPG increased the E2 level. Summarizing, it can be assumed that increased amounts of the VGVAPG during lifetime can play a certain role in calcium channel functioning in neurodegenerative diseases.

Neurochemistry International published new progress about Astrocyte; Cat; Elastin-derived peptides; IL-1β; Pparγ; VGVAPG. 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, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nijman, Taj published the artcileCost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial)., Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Atosiban; cost-effectiveness; nifedipine; perinatal outcomes; preterm birth; tocolysis.

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: â‚?4,897 versus â‚?3,376, mean difference (MD) -â‚?479 [95% confidence interval (CI) -â‚?4,327 to -â‚?016)]; multiple pregnancies: â‚?0,248 versus â‚?02,292, MD -â‚?2,044 (95% CI -â‚?1,607 to â‚?-1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

BJOG : an international journal of obstetrics and gynaecology published new progress about Atosiban; cost-effectiveness; nifedipine; perinatal outcomes; preterm birth; tocolysis. 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