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Pharmacodynamics

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https://www.readbyqxmd.com/read/28213844/self-nanoemulsified-drug-delivery-system-of-hydrochlorothiazide-for-increasing-dissolution-rate-and-diuretic-activity
#1
Cassiana Mendes, Aline Buttchevitz, Jéssica Henriques Kruger, Thiago Caon, Patricia de Oliveira Benedet, Elenara Lemos-Senna, Marcos Antônio Segatto Silva
Hydrochlorothiazide (HCTZ) is a class IV drug according to the Biopharmaceutical Classification System. This study aimed the development of self-nanoemulsifying drug delivery system (SNEDDS) for HCTZ as an approach to overcome the biopharmaceutical limitations. Pre-formulation screening and ternary phase diagrams were carried out to select the oil phase, the surfactant, and the co-surfactant as the amount of each constituent. The optimized formulations, with reduced amount of surfactant, and composed of medium chain triglycerides, Cremophor EL and Transcutol P did not affect the pH or show drug incompatibilities...
February 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28213593/randomised-double-blind-parallel-group-placebo-controlled-study-to-evaluate-the-analgesic-efficacy-and-safety-of-vvz-149-injections-for-postoperative-pain-following-laparoscopic-colorectal-surgery
#2
Srdjan S Nedeljkovic, Darin J Correll, Xiaodong Bao, Natacha Zamor, Jose L Zeballos, Yi Zhang, Mark J Young, Johanna Ledley, Jessica Sorace, Kristen Eng, Carlyle P Hamsher, Rajivan Maniam, Jonathan W Chin, Becky Tsui, Sunyoung Cho, Doo H Lee
INTRODUCTION: In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28213532/susceptibility-and-pk-pd-relationships-of-staphylococcus-aureus-strains-from-ovine-and-caprine-with-clinical-mastitis-against-five-veterinary-fluoroquinolones
#3
J M Serrano-Rodríguez, C Cárceles-García, C M Cárceles-Rodríguez, M L Gabarda, J M Serrano-Caballero, E Fernández-Varón
Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of veterinary fluoroquinolones as enrofloxacin, its metabolite ciprofloxacin, danofloxacin, difloxacin and marbofloxacin against Staphylococcus aureus strains (n=24) isolated from milk of sheep and goats affected by clinical mastitis were evaluated. The authors have used the MIC and MPC, as well as the pharmacokinetic-pharmacodynamic relationships in plasma and milk. MIC values were significantly different between drugs, unlike MPC values...
February 17, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#4
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28213088/personalized-medicine-genetic-risk-prediction-of-drug-response
#5
REVIEW
Ge Zhang, Daniel W Nebert
Pharmacogenomics (PGx), a substantial component of "personalized medicine", seeks to understand each individual's genetic composition to optimize drug therapy -- maximizing beneficial drug response, while minimizing adverse drug reactions (ADRs). Drug responses are highly variable because innumerable factors contribute to ultimate phenotypic outcomes. Recent genome-wide PGx studies have provided some insight into genetic basis of variability in drug response. These can be grouped into three categories. [a] Monogenic (Mendelian) traits include early examples mostly of inherited disorders, and some severe (idiosyncratic) ADRs typically influenced by single rare coding variants...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#6
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212385/the-effect-of-tumour-size-on-drug-transport-and-uptake-in-3-d-tumour-models-reconstructed-from-magnetic-resonance-images
#7
Wenbo Zhan, Wladyslaw Gedroyc, Xiao Yun Xu
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size...
2017: PloS One
https://www.readbyqxmd.com/read/28211545/the-effect-of-gut-microbiome-on-tolerance-to-morphine-mediated-antinociception-in-mice
#8
Minho Kang, Ryan A Mischel, Sukhada Bhave, Essie Komla, Alvin Cho, Charity Huang, William L Dewey, Hamid I Akbarali
There is growing appreciation for the importance of gastrointestinal microbiota in many physiological and pathophysiological processes. While morphine and other narcotics are the most widely prescribed therapy for moderate to severe pain clinically, they have been noted to alter microbial composition and promote bacterial translocation to other tissues. Here we examined the pharmacodynamic properties of chronic morphine in mice following bacterial depletion with oral gavage of an antibiotic cocktail (ABX). ABX significantly reduced gut bacteria and prevented chronic morphine induced increases in gut permeability, colonic mucosal destruction, and colonic IL-1β expression...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211169/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects
#9
Jin Zhou, Jarema Kochan, Ophelia Yin, Vance Warren, Cynthia Zamora, George Atiee, Joseph Pav, Yasushi Orihashi, Vijay Vashi, Victor Dishy
BACKGROUND: Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low-molecular weight compound inhibiting the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), developed as a fibrinolysis enhancer for treatment of thromboembolic diseases. OBJECTIVES: This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040 in healthy subjects...
February 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28210451/dental-management-of-patients-taking-novel-oral-anticoagulants-noas-dabigatran
#10
REVIEW
Adrian Curto, Alberto Albaladejo, Alfonso Alvarado
BACKGROUND: A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. MATERIAL AND METHODS: A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords "dabigatran", "rivaroxaban", "apixaban", "edoxaban", "new oral anticoagulants", "novel oral anticoagulants", "bleeding" and "dental treatment"...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28206886/guideline-for-monitoring-and-management-of-pediatric-patients-before-during-and-after-sedation-for-diagnostic-and-therapeutic-procedures-update-2016
#11
(no author information available yet)
The safe sedation of children for procedures requires a systematic approach that includes the following: no administration of sedating medication without the safety net of medical/dental supervision, careful presedation evaluation for underlying medical or surgical conditions that would place the child at increased risk from sedating medications, appropriate fasting for elective procedures and a balance between the depth of sedation and risk for those who are unable to fast because of the urgent nature of the procedure, a focused airway examination for large (kissing) tonsils or anatomic airway abnormalities that might increase thepotential for airway obstruction, a clear understanding of the medication's pharmacokinetic and pharmacodynamic effects and drug interactions, appropriate training and skills in airway management to allow rescue of the patient, age- and size-appropriate equipment for airway management and venous access, appropriate medications and reversal agents, sufficient numbers of staff to both carry out the procedure and monitor the patient, appropriate physiologic monitoring during and after the procedure, a properly equipped and staffed recovery area, recovery to the presedation level of consciousness before discharge from medical/dental supervision, and appropriate discharge instructions...
October 15, 2016: Pediatric Dentistry
https://www.readbyqxmd.com/read/28205455/commentary
#12
Christopher A Droege, Neil E Ernst
Obesity presents a growing challenge in critically ill patients because of variable medication pharmacokinetics and pharmacodynamics. Vasopressors used in the treatment of septic shock, including norepinephrine, are dosed using weight-based (WB) or non-weight-based (NWB) strategies. Retrospective research has evaluated the effect of total body weight and body mass index on vasopressor requirements, consequently finding that obese patients require less total vasopressor per kilogram to obtain clinical end points such as mean arterial pressure...
February 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28205039/a-pooled-analysis-of-clinical-pharmacology-trials-investigating-the-pharmacokinetic-and-pharmacodynamic-characteristics-of-fast-acting-insulin-aspart-in-adults-with-type-1-diabetes
#13
Tim Heise, Thomas R Pieber, Thomas Danne, Lars Erichsen, Hanne Haahr
BACKGROUND: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared. METHODS: The analysis included 218 adult subjects with type 1 diabetes from six randomised, double-blind, crossover trials in the faster aspart clinical development programme...
February 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28205025/the-multistate-tuberculosis-pharmacometric-model-a-semi-mechanistic-pharmacokinetic-pharmacodynamic-model-for-studying-drug-effects-in-an-acute-tuberculosis-mouse-model
#14
Chunli Chen, Fatima Ortega, Joaquin Rullas, Laura Alameda, Iñigo Angulo-Barturen, Santiago Ferrer, Ulrika Sh Simonsson
The Multistate Tuberculosis Pharmacometric (MTP) model, a pharmacokinetic-pharmacodynamic disease model, has been used to describe the effects of rifampicin on Mycobacterium tuberculosis (M. tuberculosis) in vitro. The aim of this work was to investigate if the MTP model could be used to describe the rifampicin treatment response in an acute tuberculosis mouse model. Sixty C57BL/6 mice were intratracheally infected with M. tuberculosis H37Rv strain on Day 0. Fifteen mice received no treatment and were sacrificed on Days 1, 9 and 18 (5 each day)...
February 15, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28203684/crushed-sublingual-versus-oral-ticagrelor-administration-strategies-in-patients-with-unstable-angina-a-pharmacokinetic-pharmacodynamic-study
#15
Piotr Niezgoda, Joanna Sikora, Malwina Barańska, Adam Sikora, Katarzyna Buszko, Emilia Siemińska, Michał Piotr Marszałł, Jolanta M Siller-Matula, Bernd Jilma, Dimitrios Alexopoulos, Tomasz Fabiszak, Jacek Kubica
Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28202791/establishment-and-use-of-epidemiological-cutoff-values-for-molds-and-yeasts-using-the-clinical-and-laboratory-standards-institute-m57-standard
#16
Shawn R Lockhart, Mahmoud A Ghannoum, Barbara D Alexander
Breakpoints are used to predict whether an antifungal agent will be clinically effective against a particular fungal isolate. They are based on a combination of MIC values, pharmacokinetic/pharmacodynamic values and clinical outcome data. For many fungus/antifungal combinations this data will never be available. For these combinations Epidemiological Cutoff Values (ECVs) provide a methodology to categorize isolates as either wild type or non-wild type. This review defines ECVs, explains how they are generated using the CLSI methodology in standard M57, and describes how they can be used in clinical practice...
February 15, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28202527/-18f-2s-4r-4-fluoroglutamine-pet-detects-glutamine-pool-size-changes-in-triple-negative-breast-cancer-in-response-to-glutaminase-inhibition
#17
Rong Zhou, Austin R Pantel, Shihong Li, Brian P Lieberman, Karl Ploessl, Hoon Choi, Eric Blankemeyer, Hsiaoju Lee, Hank Kung, Robert H Mach, David Mankoff
Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution 1H magnetic resonance spectroscopy (MRS)...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#18
REVIEW
L Oni, D B Hawcutt, M A Turner, M W Beresford, S McWilliam, C Barton, B K Park, P Murray, B Wilm, I Copple, R Floyd, M Peak, A Sharma, D J Antoine
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28202132/comparison-of-platelet-reactivity-in-black-versus-white-patients-with-acute-coronary-syndromes-after-treatment-with-ticagrelor
#19
Michael A Gaglia, Michael J Lipinski, Thibault Lhermusier, Arie Steinvil, Sarkis Kiramijyan, Shreejana Pokharel, Rebecca Torguson, Dominick J Angiolillo, Lars Wallentin, Robert F Storey, Ron Waksman
Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily...
January 25, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28202048/chemotherapy-for-primary-mediastinal-yolk-sac-tumor-in-a-patient-undergoing-chronic-hemodialysis-a-case-report
#20
Haruki Hirakawa, Chiho Nakashima, Tomomi Nakamura, Masanori Masuda, Taro Funakoshi, Shunsaku Nakagawa, Takahiro Horimatsu, Kazuo Matsubara, Manabu Muto, Shinya Kimura, Naoko Sueoka-Aragane
BACKGROUND: The safety and efficacy of chemotherapy for patients undergoing concomitant hemodialysis have not been fully established and optimal doses of anti-cancer drugs and best timing of hemodialysis remains unclear. Although chemosensitive cancers, such as germ cell tumors, treated with chemotherapy should have sufficient dose intensity maintained to achieve the desired effect, many patients with cancer undergoing hemodialysis might be under-treated because the pharmacokinetics of anti-cancer drugs in such patients remains unknown...
February 16, 2017: Journal of Medical Case Reports
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