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Pharmacodynamics

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https://www.readbyqxmd.com/read/29793098/evaluation-of-analgesic-and-anti-inflammatory-activities-of-rubia-cordifolia-l-by-spectrum-effect-relationships
#1
REVIEW
Cai-Hong Shen, Cui-Ting Liu, Xiao-Juan Song, Wei-Ya Zeng, Xiao-Ying Lu, Zuo-Liang Zheng, Jie-Pan, Ruo-Ting Zhan, Ping-Yan
The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti-inflammatory properties of RCE...
May 17, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29792841/decarboxylation-of-ang-1-7-to-ala-1-ang-1-7-leads-to-significant-changes-in-pharmacodynamics
#2
Anja Tetzner, Maura Naughton, Kinga Gebolys, Jenny Eichhorst, Esther Sala, Óscar Villacañas, Thomas Walther
The heptapeptide angiotensin (Ang)-(1-7) is part of the beneficial arm of the renin-angiotensin system. Ang-(1-7) has cardiovascular protective effects, stimulates regeneration, and opposes the often detrimental effects of Ang II. We recently identified the G protein-coupled receptors Mas and MrgD as receptors for the heptapeptide. Ala1 -Ang-(1-7) (Alamandine), a decarboxylated form of Ang-(1-7), has similar vasorelaxant effects, but has been described to only stimulate MrgD. Therefore, this study aimed to characterise the consequences of the lack of the carboxyl group in amino acid 1 on intracellular signalling and to identify the receptor fingerprint for Ala1 -Ang-(1-7)...
May 21, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29792287/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-glpg1690-a-novel-autotaxin-inhibitor-to-treat-idiopathic-pulmonary-fibrosis-flora-a-phase-2a-randomised-placebo-controlled-trial
#3
Toby M Maher, Ellen M van der Aar, Olivier Van de Steen, Lisa Allamassey, Julie Desrivot, Sonia Dupont, Liesbeth Fagard, Paul Ford, Ann Fieuw, Wim Wuyts
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. People with IPF have increased concentrations of autotaxin in lung tissue and lysophosphatidic acid (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is a novel, potent, selective autotaxin inhibitor with good oral exposure. We explored the effects of GLPG1690 in patients with IPF. METHODS: This was a randomised, double-blind, placebo-controlled phase 2a study done in 17 centres in Italy, Ukraine and the UK...
May 18, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29792125/characteristics-of-apixaban-treated-patients-evaluation-of-the-dose-prescribed-and-the-persistence-of-treatment-a-cohort-study-in-catalonia
#4
Ainhoa Gomez-Lumbreras, Jordi Cortes, Maria Giner-Soriano, M Angeles Quijada-Manuitt, Rosa Morros
BACKGROUND: Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. OBJECTIVES: (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29792121/abcg2-polymorphism-rs2231142-and-hypothyroidism-in-metastatic-renal-cell-carcinoma-patients-treated-with-sunitinib
#5
Emilie Werbrouck, Julie Bastin, Diether Lambrechts, Annelies Verbiest, Thomas Van Brussel, Evelyne Lerut, Jean-Pascal Machiels, Vincent Verschaeve, Vincent Richard, Philip R Debruyne, Brigitte Decallonne, Patrick Schöffski, Oliver Bechter, Pascal Wolter, Benoit Beuselinck
Background and aim Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) cause significant adverse events including thyroid dysfunction, mainly hypothyroidism, in a considerable proportion of patients. In a series of metastatic renal cell carcinoma (mRCC) patients treated with sunitinib, we aimed to study the correlation between hypothyroidism and single nucleotide polymorphisms (SNPs) in genes involved in sunitinib pharmacokinetics and pharmacodynamics. Patients and methods We included 79 mRCC patients who started sunitinib between November 2005 and March 2016...
May 23, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29791829/burosumab-therapy-in-children-with-x-linked-hypophosphatemia
#6
Thomas O Carpenter, Michael P Whyte, Erik A Imel, Annemieke M Boot, Wolfgang Högler, Agnès Linglart, Raja Padidela, William Van't Hoff, Meng Mao, Chao-Yin Chen, Alison Skrinar, Emil Kakkis, Javier San Martin, Anthony A Portale
BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range...
May 24, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29790586/pharmacokinetic-and-pharmacodynamic-model-for-analysis-of-adalimumab-administered-for-crohn-s-disease
#7
Koji Kimura, Atsushi Yoshida, Risa Takayanagi, Yasuhiko Yamada
Adalimumab (ADA) is used as a therapeutic agent for Crohn's disease (CD). Although that dosage regimen has been established through clinical trial experience, it has not been analyzed theoretically. In the present study, we analyzed of sequential changes of the Crohn's disease activity index (CDAI) after repeated administrations of ADA using a pharmacokinetic and pharmacodynamic model. In addition, we analyzed the validity of the dosage regimen, and potential efficacy gained by increasing the dose and reducing the interval of administration...
May 23, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29790581/the-pharmacokinetics-pharmacodynamics-and-tolerability-of-pur0200-a-novel-tiotropium-formulation-in-chronic-obstructive-pulmonary-disease
#8
Dave Singh, Arjun Ravi, Katie Kane, Tess Schmalbach, David L Hava
AIMS: PUR0200 is a tiotropium bromide formulation engineered with the iSPERSE dry powder delivery technology. PUR0200 is being developed as a bioequivalent alternative to tiotropium bromide delivered using Spiriva® HandiHaler® (HH). We investigated the bronchodilator effects, pharmacokinetics and safety of PUR0200 in COPD patients. METHODS: This was a randomised, placebo-controlled, crossover study with different PUR0200 doses and the comparator tiotropium HH...
May 23, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29789008/pharmacological-effects-of-n-2-2-2-2-6-dichlorophenyl-amino-phenyl-acetyl-oxy-ethyl-hyaluronamide-diclofenac-etalhyaluronate-si-613-a-novel-sodium-hyaluronate-derivative-chemically-linked-with-diclofenac
#9
Keiji Yoshioka, Tomochika Kisukeda, Ryoji Zuinen, Yosuke Yasuda, Kenji Miyamoto
BACKGROUND: Osteoarthritis (OA) is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have investigated the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), which is a potentially safer and more effective treatment for OA knee pain. In this study, we evaluated the pharmacological effects of SI-613 in experimental arthritis models. METHODS: We compared the analgesic and anti-inflammatory effects of intra-articularly administered SI-613, hyaluronic acid (HA), and of orally administered diclofenac sodium (DF-Na) in rat silver nitrate-induced arthritis model and rabbit antigen-induced arthritis model...
May 22, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29788882/impact-of-drug-metabolism-pharmacokinetics-and-their-relevance-upon-taxus-based-drug-development
#10
Da-Cheng Hao, Guang-Bo Ge, Ping Wang, Ling Yang
Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI)...
May 22, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788871/biologics-for-the-treatment-of-juvenile-idiopathic-arthritis
#11
Dimitri Poddighe, Micol Romano, Maurizio Gattinara, Valeria Gerloni
Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate specific mechanisms of the immune systems, such as TNF-α, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidences regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29788512/adequacy-of-fixed-dose-heparin-infusions-for-venous-thromboembolism-prevention-after-microsurgical-procedures
#12
Corinne M Bertolaccini, Ann Marie B Prazak, Jayant Agarwal, Isak A Goodwin, W Bradford Rockwell, Christopher J Pannucci
BACKGROUND:  In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments...
May 22, 2018: Journal of Reconstructive Microsurgery
https://www.readbyqxmd.com/read/29788329/pharmacokinetic-and-pharmacodynamic-properties-of-metronidazole-in-pediatric-patients-with-acute-appendicitis-a-prospective-study
#13
Jason Child, Xinhui Chen, Rakesh D Mistry, Stig Somme, Christine MacBrayne, Peter L Anderson, Ronald N Jones, Sarah K Parker
Background: Metronidazole is traditionally dosed every 6-8 hours even though in adults it has a long half-life, concentration-dependent killing, and 3-hour postantibiotic effect. Based on this logic, some pediatric hospitals adopted once-daily dosing for appendicitis, despite limited pharmacokinetics-pharmacodynamics (PK/PD) in children. We studied pediatric patients with appendicitis given metronidazole once daily to determine whether this dosing would meet target area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio of ≥70 for Bacteroides fragilis...
May 16, 2018: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/29788155/phase-i-study-of-the-checkpoint-kinase-1-inhibitor-gdc-0575-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#14
A Italiano, J R Infante, G I Shapiro, K N Moore, P M LoRusso, E Hamilton, S Cousin, M Toulmonde, S Postel-Vinay, S Tolaney, E M Blackwood, S Mahrus, F V Peale, X Lu, A Moein, J Epler, K DuPree, M Tagen, E R Murray, J L Schutzman, J O Lauchle, A Hollebecque, J-C Soria
Background: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed...
February 23, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29786965/l-and-d-threo-ethylphenidate-concentrations-pharmacokinetics-and-pharmacodynamics-in-horses
#15
Heather K Knych, Dan S McKemie, Kelsey Seminoff, Petra Hartmann, Lynn Hovda, Dionne Benson
Ethylphenidate is a psychostimulant and analogue of the commonly prescribed compound, methylphenidate (Ritalin®). There are a limited number of studies describing the disposition and pharmacologic/toxicological effects of ethylphenidate in any species. The abuse potential in equine athletes along with the limited data available regarding administration in horses necessitates further study. The objectives of the current study were to describe drug concentrations, develop an analytical method that could be used to regulate its use and describe the pharmacodynamic effects of ethylphenidate in horses...
May 22, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29786964/a-thorough-qt-qtc-study-with-laquinimod-a-novel-immunomodulator-in-development-for-multiple-sclerosis-and-huntington-disease
#16
Ofer Spiegelstein, Dorit Mimrod, Laura Rabinovich, Eli Eyal, Craig Sprenger, Anna Elgart, Emil Samara, Joel Morganroth
In this randomized double-blind study, 4 groups of healthy subjects (50 per arm) participated to evaluate the effect of laquinimod, an oral treatment in development for multiple sclerosis and Huntington disease, on the QTc interval. Subjects received a dose of either 0.6 or 1.2 mg/day laquinimod for 14 days, placebo for 14 days, or 13 days of placebo followed by a dose of 400 mg moxifloxacin on day 14. Continuous 12-lead electrocardiograms were recorded on day -1 (baseline) and days 14 to 17,  and quadruplicate electrocardiograms were extracted at predefined time points...
May 22, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#17
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29785888/the-impact-of-oprm1-s-genetic-polymorphisms-on-methadone-maintenance-treatment-in-opioid-addicts-a-systematic-review
#18
Bilel Oueslati, Olfa Moula, Rim Ghachem
AIM: Methadone is a long-acting opioid receptor agonist. It is prescribed to patients with opioid-related use disorders. The OPRM1 gene encodes for methadone's main receptor. It appears that polymorphisms in OPRM1 may affect the efficacy of methadone maintenance treatment (MMT). OBJECTIVE: Our purpose was to identify all relevant published papers dealing with the impact ofOPRM1's SNPs  on MMT's efficacy and to summarize results in order to evaluate the relevance of conducting pretherapeutic genotyping in opioid addicts prior to the onset of MMT...
May 22, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29785574/in-situ-nanostructured-hydrogel-of-resveratrol-for-brain-targeting-in-vitro-in-vivo-characterization
#19
Amarjitsing Rajput, Aditi Bariya, Ahmed Allam, Sarah Othman, Shital B Butani
The purpose of conducting the present research work was to develop resveratrol nanostructured in situ gel for the treatment of Alzheimer's disease. Resveratrol loaded lipid carrier was prepared by melt emulsification-probe sonication method, and the final product was evaluated for particle size (132 ± 11.90 nm), polydispersity index (0.209 ± 0.005), zeta potential (- 23 ± 3.79 mV), drug loading (9.26 ± 3.79%), and entrapment efficiency (74 ± 11.40%). Following incorporation of the resveratrol nanostructured lipid carrier in gellan gum and xanthan gum, in situ gel was formulated and characterized...
May 21, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29785570/phase-1b-investigation-of-the-mek-inhibitor-binimetinib-in-patients-with-advanced-or-metastatic-biliary-tract-cancer
#20
R S Finn, D H Ahn, M M Javle, B R Tan, C D Weekes, J C Bendell, A Patnaik, G N Khan, D Laheru, R Chavira, J Christy-Bittel, E Barrett, M B Sawyer, Tanios S Bekaii-Saab
Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in patients who received ≤1 line of therapy for advanced BTC was conducted after determination of the maximum tolerated dose in this Phase 1 trial. Patients received binimetinib 60 mg twice daily...
May 22, 2018: Investigational New Drugs
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