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Pharmacodynamics

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https://www.readbyqxmd.com/read/27913535/reversing-vitamin-k-antagonists-making-the-old-new-again
#1
Sabine Eichinger
Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific interaction with the vitamin K cycle, and hence interference with hepatic synthesis of vitamin K-dependent coagulation factors. Monitoring the anticoagulant effect of VKAs by assessing the patient's international normalized ratio (INR) is essential because complications are closely related to the intensity of anticoagulation. Treatment with VKAs contains a substantial risk of bleeding with a high case fatality rate...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912876/in-vitro-and-ex-vivo-activity-of-an-azadirachta-indica-a-juss-seed-kernel-extract-on-early-sporogonic-development-of-plasmodium-in-comparison-with-azadirachtin-a-its-most-abundant-constituent
#2
Nisha Dahiya, Giuseppina Chianese, Solomon Mequanente Abay, Orazio Taglialatela-Scafati, Fulvio Esposito, Giulio Lupidi, Massimo Bramucci, Luana Quassinti, George Christophides, Annette Habluetzel, Leonardo Lucantoni
BACKGROUND: NeemAzal(®) (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#3
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27910712/development-of-a-nanogel-formulation-for-transdermal-delivery-of-tenoxicam-a-pharmacokinetic-pharmacodynamic-modeling-approach-for-quantitative-prediction-of-skin-absorption
#4
Mohammed H Elkomy, Shahira F El Menshawe, Hussein M Eid, Ahmed M A Ali
This study investigates potentials of solid lipid nanoparticles (SLN) based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetics-pharmacodynamics (PK-PD) modeling approach for predicting concentration-time profile in skin. A 2(3) factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan induced rat paw edema test...
December 2, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#5
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27909752/erratum-to-a-literature-review-of-the-pharmacokinetics-and-pharmacodynamics-of-dobutamine-in-neonates
#6
Liam Mahoney, Geetika Shah, David Crook, Hector Rojas-Anaya, Heike Rabe
No abstract text is available yet for this article.
December 1, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27908273/pharmacokinetic-and-pharmacodynamic-features-of-nanoemulsion-following-oral-intravenous-topical-and-nasal-route
#7
Hira Choudhury, Bapi Gorain, Bappaditya Chatterjee, Uttam Kumar Mandal, Pinaki Sengupta, Rakesh Kumar Tekade
Most of the active pharmaceutical ingredients discovered recently in pharmaceutical field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra subject variability. Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#8
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27907978/comparison-of-the-single-dose-pharmacokinetics-pharmacodynamics-and-safety-of-two-novel-oral-formulations-of-dimethandrolone-undecanoate-dmau-a-potential-oral-male-contraceptive
#9
R Ayoub, S T Page, R S Swerdloff, P Y Liu, J K Amory, A Leung, L Hull, D Blithe, A Christy, J H Chao, W J Bremner, C Wang
Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation...
December 1, 2016: Andrology
https://www.readbyqxmd.com/read/27907971/-interpretation-of-bacterial-susceptibility-resistance-to-antibiotics
#10
Milan Kolář
Bacterial resistance may be defined from a microbiological, clinical and pharmacological perspective. Microbiological resistance refers to the presence of genetic information coding for the relevant mechanism of resistance of a bacterium to a particular antibiotic. In case of clinical interpretation, breakpoints are of key importance as their role is to distinguish bacterial pathogens in which successful therapy is highly probable from isolates with a high likelihood of failure. However, it is questionable whether this approach is suitable for all patients, particularly those receiving intensive care for life-threatening infections...
September 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27907963/optimizing-medication-outcomes-in-neurocritical-care-focus-on-clinical-pharmacology
#11
Denise H Rhoney, Kathryn Morbitzer, Jimmi Hatton-Kolpek
Drug dosing in neurocritically ill patients presents enormous challenges for clinicians due to the complex pathophysiological alterations. These alterations are dynamic both between and within patients. Unpredictable exposure from standard dosing regimens, which were extrapolated to intensive care unit patients from healthy volunteer studies, may influence medication outcomes. Knowledge of potential alterations in pharmacokinetics/pharmacodynamics in these patients could be applied to maximize the clinical response and minimize adverse effects...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27907033/normalization-of-patient-identified-plasma-biomarkers-in-smn%C3%AE-7-mice-following-postnatal-smn-restoration
#12
W David Arnold, Sandra Duque, Chitra C Iyer, Phillip Zaworski, Vicki L McGovern, Shannon J Taylor, Katharine M von Herrmann, Dione T Kobayashi, Karen S Chen, Stephen J Kolb, Sergey V Paushkin, Arthur H M Burghes
INTRODUCTION AND OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function...
2016: PloS One
https://www.readbyqxmd.com/read/27906953/what-s-tramadol-got-to-do-with-it-a-case-report-of-rebound-hypoglycemia-a-reappraisal-and-review-of-potential-mechanisms
#13
Charles A Odonkor, Akhil Chhatre
BACKGROUND: Tramadol has gained traction as an analgesic of choice among pain practicing physicians. However some concerns regarding a previously unlabeled adverse reaction - hypoglycemia - have cast it in a dim light. Prior reports have noted an associated risk of hospitalization for hypoglycemia after tramadol use, but whether tramadol is the main causal agent is poorly understood and the underlying mechanisms are not well delineated. We present a unique case of rebound hypoglycemia as a variation of the theme of tramadol's adverse effect profile in a patient with type 1 diabetes mellitus, and reappraise potential mechanisms underlying this underappreciated phenomenon...
November 2016: Pain Physician
https://www.readbyqxmd.com/read/27906418/assessment-of-celecoxib-poly-lactic-co-glycolic-acid-nanoformulation-on-drug-pharmacodynamics-and-pharmacokinetics-in-rats
#14
S Harirforoosh, K O West, D E Murrell, J W Denham, P C Panus, G A Hanley
OBJECTIVE:  Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP)...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27905678/a-phase-i-ii-trial-of-at9283-a-selective-inhibitor-of-aurora-kinase-in-children-with-relapsed-or-refractory-acute-leukemia-challenges-to-run-early-phase-clinical-trials-for-children-with-leukemia
#15
B Vormoor, G J Veal, M J Griffin, A V Boddy, J Irving, L Minto, M Case, U Banerji, K E Swales, J R Tall, A S Moore, M Toguchi, G Acton, K Dyer, C Schwab, C J Harrison, J D Grainger, D Lancaster, P Kearns, D Hargrave, J Vormoor
Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27905583/intracellular-water-an-overlooked-drug-target-cisplatin-impact-in-cancer-cells-probed-by-neutrons
#16
M P M Marques, A L M Batista de Carvalho, V Garcia Sakai, L Hatter, L A E Batista de Carvalho
The first neutron scattering study on human nucleated cells is reported, addressing the subject of solvent-slaving to a drug by probing intracellular water upon drug exposure. Inelastic and quasi-elastic neutron scattering spectroscopy with isotope labelling was applied for monitoring interfacial water response to the anticancer drug cisplatin, in the low prognosis human metastatic breast cancer cells MDA-MB-231. Optical vibrational data were also obtained for lyophilised cells. Concentration-dependent dynamical changes evidencing a progressive mobility reduction were unveiled between untreated and cisplatin-exposed samples, concurrent with variations in the native organisation of water molecules within the intracellular medium as a consequence of drug action...
December 1, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27905408/limitations-of-mic-as-sole-metric-of-pharmacodynamic-response-across-the-range-of-antimicrobial-susceptibilities-within-a-single-bacterial-species
#17
Xuesong Wen, Ronette Gehring, Andrea Stallbaumer, Jim E Riviere, Victoriya V Volkova
The minimum inhibitory concentration (MIC) of an antimicrobial drug for a bacterial pathogen is used as a measure of the bacterial susceptibility to the drug. However, relationships between the antimicrobial concentration, bacterial susceptibility, and the pharmacodynamic (PD) inhibitory effect on the bacterial population are more complex. The relationships can be captured by multi-parameter models such as the Emax model. In this study, time-kill experiments were conducted with a zoonotic pathogen Pasteurella multocida and the fluoroquinolone enrofloxacin...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904008/pharmacodynamics-biomarkers-application-and-considerations-in-clinical-development
#18
Seiji Mito, Masaki Sakai, Masayuki Suzuki
No abstract text is available yet for this article.
2016: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/27903752/hexim1-as-a-robust-pharmacodynamic-marker-for-monitoring-target-engagement-of-bet-family-bromodomain-inhibitors-in-tumors-and-surrogate-tissues
#19
Xiaoyu Lin, Xiaoli Huang, Tamar Uziel, Paul Hessler, Daniel H Albert, Lisa A Roberts-Rapp, Keith F McDaniel, Warren M Kati, Yu Shen
An increasing number of BET family protein inhibitors have recently entered clinical trials. It has been reported that attempts of monitoring target engagement of the BET bromodomain inhibitor OTX015 using literature-described putative pharmacodynamic (PD) markers such as c-Myc, BRD2, etc. failed to detect PD marker responses in AML patients treated at active dose and those with clinical responses. Here we report the identification and characterization of HEXIM1 and other genes as robust PD markers for BET inhibitors...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903151/how-to-manage-the-obese-patient-with-cancer
#20
Andrew G Renehan, Michelle Harvie, Ramsey I Cutress, Michael Leitzmann, Tobias Pischon, Sacha Howell, Anthony Howell
Purpose Obesity (body mass index [BMI] ≥ 30 kg/m(2)) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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