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Pharmacodynamics

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https://www.readbyqxmd.com/read/28102083/development-and-characterization-of-morin-hydrate-loaded-microemulsion-for-the-management-of-alzheimer-s-disease
#1
Dheeraj Sharma, Manpreet Singh, Punnet Kumar, Vir Vikram, Neeraj Mishra
The aim of this study is to prepare and characterize intranasal delivery of morin hydrate loaded microemulsion for the management of Alzheimer's diseases. After intranasal delivery, brain and blood drug concentrations were found to be higher for optimized morin hydrate loaded microemulsion as compared to plain morin hydrate. Significant (P < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of morin hydrate loaded microemulsion as compared to sham control group...
January 19, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28101885/what-is-the-true-in%C3%A2-vitro-potency-of-oxytetracycline-for-the-pig-pneumonia-pathogens-actinobacillus-pleuropneumoniae-and-pasteurella-multocida
#2
L Dorey, S Hobson, P Lees
The pharmacodynamics of oxytetracycline was determined for pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Indices of potency were determined for the following: (i) two matrices, broth and pig serum; (ii) five overlapping sets of twofold dilutions; and (iii) a high strength starting culture. For A. pleuropneumoniae, minimum inhibitory concentration (MIC) was similar for the two matrices, but for P. multocida, differences were marked and significantly different. MIC and minimum bactericidal concentration (MBC) serum: broth ratios for A...
January 18, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28101836/a-review-of-clinical-outcomes-associated-with-two-meropenem-dosing-strategies
#3
REVIEW
Kyle John Wilby, Ziad Ghantous Nasr, Shereen Elazzazy, Tim T Y Lau, Anas Hamad
Meropenem is a carbapenem antibiotic that exhibits time-dependent bactericidal activity, traditionally dosed intravenously at 1 g every 8 h. In order to maximize its pharmacodynamic activity and reduce costs, an alternative regimen employed by many institutions is 500 mg every 6 h. The objective of this review was to summarize and evaluate published literature comparing clinical outcomes associated with these two meropenem dosing regimens. The literature was searched up to October 2016 using the MEDLINE, EMBASE, and Google Scholar databases...
January 18, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#4
Charvi Nanavati, Donald E Mager
PURPOSE: To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. METHODS: U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures...
January 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28101726/development-of-timolol-loaded-galactosylated-chitosan-nanoparticles-and-evaluation-of-their-potential-for-ocular-drug-delivery
#5
Ruobing Zhao, Jing Li, Jingyi Wang, Zhenya Yin, Yongtao Zhu, Wei Liu
This study was conducted to develop timolol maleate (TM)-loaded galactosylated chitosan (GC) nanoparticles (NPs) (TM-GC-NPs) followed by optimization via a four-level and three-factor Box-Behnken statistical experimental design. The optimized nanoparticles showed a particle size of 213.3 ± 6.83 nm with entrapment efficiency of 38.58 ± 1.31% and drug loading of 17.72 ± 0.28%. The NPs were characterized with respect to zeta potential, pH, surface morphology, and differential scanning calorimetry (DSC)...
January 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28101651/eslicarbazepine-acetate-its-effectiveness-as-adjunctive-therapy-in-clinical-trials-and-open-studies
#6
REVIEW
S D Shorvon, E Trinka, B J Steinhoff, M Holtkamp, V Villanueva, J Peltola, E Ben-Menachem
Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug that is approved as adjunctive therapy in adults with focal-onset seizures. Following oral administration, ESL is rapidly metabolized to its active metabolite, eslicarbazepine, which acts primarily by enhancing slow inactivation of voltage-gated sodium channels. The efficacy and safety/tolerability of ESL in the adjunctive setting were established in a comprehensive Phase III program (n = 1702 randomized patients) and this evidence has been supported by several open studies (n = 864)...
January 18, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28101342/pharmacodynamic-analysis-of-target-controlled-infusion-of-propofol-in-patients-with-hepatic-insufficiency
#7
Jing-Ru Pan, Jun Cai, Shao-Li Zhou, Qian-Qian Zhu, Fei Huang, Yi-Han Zhang, Xin-Jin Chi, Zi-Qing Hei
The effect of liver dysfunction on target-controlled infusion (TCI) of propofol remains poorly documented. The pharmacodynamic performance of propofol TCI was evaluated in a cohort of Chinese patients with hepatic insufficiency. Fifty-three patients with hepatic insufficiency were enrolled in the current prospective, observational study. Anesthesia was induced with propofol via TCI to a plasma concentration of 3 µg/ml. Following loss of consciousness (LOC), fentanyl and cisatracurium were administered. Pharmacodynamic parameters were recorded during TCI, including time to LOC, bispectral index (BIS), heart rate (HR) and blood pressure...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28101322/brexpiprazole-and-cariprazine-distinguishing-two-new-atypical-antipsychotics-from-the-original-dopamine-stabilizer-aripiprazole
#8
REVIEW
Joshua S Frankel, Thomas L Schwartz
BACKGROUND: Brexpiprazole and cariprazine are the latest US Food and Drug Administration approved atypical antipsychotics available in the United States. Both function as partial agonists of the dopamine-2 receptor (D2R), a mechanism of action shared with aripiprazole. However, all three differ in their affinities for the D2R as well as for serotonin receptors (5-HTRs). This paper seeks to delineate these pharmacodynamic and clinical differences amongst the three dopamine partial agonist atypical antipsychotic drugs...
January 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28099979/milrinone-pharmacokinetics-and-pharmacodynamics-in-neonates-with-persistent-pulmonary-hypertension-of-the-newborn
#9
Annie Giaccone, Athena F Zuppa, Beena Sood, Meryl S Cohen, Michael L O'Byrne, Ganesh Moorthy, Amit Mathur, Haresh Kirpalani
Objective To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design Randomized, open label pilot study. Setting Multicenter; level 3 and level 4 neonatal intensive care units. Patients Six infants ≥34 weeks' gestational age and <10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0...
January 18, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28099525/polyethylene-glycol-camouflaged-earthworm-hemoglobin
#10
Vivek P Jani, Alborz Jelvani, Selamawit Moges, Parimala Nacharaju, Camille Roche, David Dantsker, Andre Palmer, Joel M Friedman, Pedro Cabrales
Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris...
2017: PloS One
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#11
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28098426/dapagliflozin-in-patients-with-type-1-diabetes-a-post-hoc-analysis-of-the-effect-of-insulin-dose-adjustments-on-24-hour-continuously-monitored-mean-glucose-and-fasting-beta-hydroxybutyrate-levels-from-a-phase-iia-pilot-study
#12
Robert R Henry, Paresh Dandona, Jeremy Pettus, Sunder Mudaliar, John Xu, Lars Hansen
AIMS: To investigate the effects of total daily insulin dose (TDD) reductions on 24-hour continuously monitored mean glucose and fasting beta-hydroxybutyrate (a marker for diabetic ketosis/ketoacidosis [DKA]) using patient-level data from a 14-day, pilot study of dapagliflozin in type 1 diabetes. MATERIALS AND METHODS: Exploratory correlation analysis was performed post-hoc to determine the relationship between change in TDD and a) 24-hour mean glucose (by continuous glucose monitoring) and b) fasting beta-hydroxybutyrate, in 70 patients with type 1 diabetes receiving insulin and dapagliflozin (1-, 2...
January 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28097886/reagent-free-lc-ms-ms-based-pharmacokinetic-quantification-of-polyhistidine-tagged-therapeutic-proteins
#13
Jianxia Shi, Jing Man Wong, Ji Ma, Tiffany Dickerson, Colin Hall, Dan A Rock, Timothy J Carlson
AIM: Immobilized metal ion affinity chromatography is widely employed for purifying polyhistidine-tagged recombinant proteins from cell lysates. The technique can be applied for quantification of therapeutic proteins in biological matrices by LC-MS/MS. RESULTS: A protein reagent-free workflow was developed for quantifying polyhistidine-tagged proteins by LC-MS/MS. The workflow includes target protein enrichment by immobilized metal ion affinity chromatography, on-bead trypsin digestion and quantification of signature peptides by LC-MS/MS...
January 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28097665/pharmacokinetics-and-selected-pharmacodynamics-of-romifidine-following-low-dose-intravenous-administration-in-combination-with-exercise-to-quarter-horses
#14
H K Knych, S D Stanley, D S McKemie, S J Steinmetz
Romifidine is an alpha-2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low-dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography-tandem mass spectrometry assay that is currently employed in many drug testing laboratories...
January 17, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28097639/risk-of-bleeding-and-repeated-bleeding-events-in-prasugrel-treated-patients-a-review-of-data-from-the-japanese-prasfit-studies
#15
REVIEW
Masakatsu Nishikawa, Takaaki Isshiki, Takeshi Kimura, Hisao Ogawa, Hiroyoshi Yokoi, Shunichi Miyazaki, Yasuo Ikeda, Masato Nakamura, Yuko Tanaka, Shigeru Saito
Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3...
January 17, 2017: Cardiovascular Intervention and Therapeutics
https://www.readbyqxmd.com/read/28097633/meropenem-dosing-based-on-a-population-pharmacokinetic-pharmacodynamic-model-in-elderly-patients-with-infection-of-the-lower-respiratory-tract
#16
Qing-Tao Zhou, Bei He, Ning Shen, Ying Liang, Li-Na Sun
BACKGROUND: Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli. OBJECTIVE: We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI. METHODS: In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG)...
January 17, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28097385/two-phase-1-dose-escalation-studies-exploring-multiple-regimens-of-litronesib-ly2523355-an-eg5-inhibitor-in-patients-with-advanced-cancer
#17
Jeffrey R Infante, Amita Patnaik, Claire F Verschraegen, Anthony J Olszanski, Montaser Shaheen, Howard A Burris, Anthony W Tolcher, Kyriakos P Papadopoulos, Muralidhar Beeram, Scott M Hynes, Jennifer Leohr, Aimee Bence Lin, Lily Q Li, Anna McGlothlin, Daphne L Farrington, Eric H Westin, Roger B Cohen
PURPOSE: This first-in-human report examined the recommended Phase 2 dose and schedule of litronesib, a selective allosteric kinesin Eg5 inhibitor. METHODS: Two concurrent dose-escalation studies investigated litronesib across the dose range of 0.125-16 mg/m(2)/day, evaluating the following schedules of administration on a 21-day cycle: Days 1, 2, 3; Days 1, 5, 9; Days 1, 8; Days 1, 5; or Days 1, 4, with or without pegfilgrastim. Best overall response was defined per Response Evaluation Criteria in Solid Tumors (RECIST Version 1...
January 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#18
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28097012/pharmacokinetics-and-pharmacodynamics-of-antibiotics-in-critically-ill-acute-kidney-injury-patients
#19
REVIEW
Welder Zamoner, Fernanda M de Freitas, Durval S S Garms, Mariele Gobo de Oliveira, André L Balbi, Daniela Ponce
Sepsis is the most common cause of death in critically ill patients and is associated with multiorgan failure, including acute kidney injury (AKI). This situation can require acute renal support and increase mortality. Therefore, it is essential to administer antimicrobials in doses that achieve adequate serum levels, avoiding both overdosing and drug toxicity as well as underdosing and the risk of antibiotic resistance and higher mortality. Currently, there are no validated guidelines on antibiotic dose adjustments in septic patients with AKI...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28097000/biased-small-molecule-ligands-for-selective-inhibition-of-hiv-1-cell-entry-via-ccr5
#20
Christian Berg, Katja Spiess, Hans R Lüttichau, Mette M Rosenkilde
Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout...
December 2016: Pharmacology Research & Perspectives
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