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https://www.readbyqxmd.com/read/28730281/pk-pd-studies-on-non-selective-pde-inhibitors-in-rats-using-camp-as-a-marker-of-pharmacological-response
#1
Artur Świerczek, Elżbieta Wyska, Sebastian Baś, Marta Woyciechowska, Jacek Mlynarski
In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg(-1), i...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28716651/significance-of-a-to-i-rna-editing-of-transcripts-modulating-pharmacokinetics-and-pharmacodynamics
#2
REVIEW
Masataka Nakano, Miki Nakajima
RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation...
July 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28709989/evaluating-biapenem-dosage-regimens-in-intensive-care-unit-patients-with-pseudomonas-aeruginosa-infections-a-pharmacokinetic-pharmacodynamic-analysis-using-monte-carlo-simulation
#3
Yongfu Hang, Yafang Chen, Ling Xue, Shusen Sun, Long Liu, Jie Gao, Cheng Xie, Xianfeng Zhang, Jianguo Zhu, Jun Jin, Liyan Miao
This study sought to both identify optimal dosage regimens and estimate pharmacokinetic/pharmacodynamics characteristics of short-infusion (SI) versus extended-infusion (EI) for the use of biapenem against Pseudomonas aeruginosa infections in Chinese Intensive Care patients. A total of 85 strains of P. aeruginosa were collected, and the minimum inhibitory concentration (MIC) of biapenem was measured by the serial two-fold agar dilution method. We designed four frequently used clinical regimens: biapenem 300mg I...
July 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28706488/postnatal-maturation-of-the-glomerular-filtration-rate-in-conventional-growing-piglets-as-potential-juvenile-animal-model-for-preclinical-pharmaceutical-research
#4
Elke Gasthuys, Mathias Devreese, Joske Millecam, Stanislas Sys, Katrien Vanderperren, Joris Delanghe, Johan Vande Walle, Marjolein Heyndrickx, Siska Croubels
Adequate animal models are required to study the preclinical pharmacokinetics (PK), pharmacodynamics (PD) and safety of drugs in the pediatric subpopulation. Over the years, pigs were presented as a potential animal model, since they display a high degree of anatomical and physiological similarities with humans. To assess the suitability of piglets as a preclinical animal model for children, the ontogeny and maturation processes of several organ systems have to be unraveled and compared between both species...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28701951/pharmacokinetic-pharmacodynamic-modeling-of-tulathromycin-against-pasteurella-multocida-in-a-porcine-tissue-cage-model
#5
Qiaoyi Zhou, Guijun Zhang, Qin Wang, Wenguang Liu, Yan Huang, Pengling Yu, Yanqin Li, Huanzhong Ding, Binghu Fang
Tulathromycin, a macrolide antibiotic, is used for the treatment of respiratory disease in cattle and swine. The aim of our study was to investigate the in vitro and ex vivo activities of tulathromycin in serum, (non-inflamed) transudate, and (inflamed) exudate against Pasteurella multocida in piglets. The pharmacokinetics properties of tulathromycin were studied for serum, transudate, and exudate using a tissue cage model. In vitro antibiotic susceptibility of P. multocida and dynamic time-kill curve experiments over eight tulathromycin concentrations were determined...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28700987/impact-of-intravenous-p2y12-receptor-inhibition-with-cangrelor-in-patients-presenting-with-acute-coronary-syndrome-and-cardiogenic-shock-a-case-series
#6
Michal Droppa, Oliver Borst, Dominik Rath, Karin Müller, Meinrad Gawaz, Deepak L Bhatt, Tobia Geisler
BACKGROUND/AIMS: Patients with acute coronary syndromes (ACS) presenting with cardiogenic shock (CS) are at particular risk for death and adverse cardiac events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to decreased organ hypoperfusion or hypothermia and challenges regarding oral administration contribute to this risk. We report a single center experience regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients with CS treated with percutaneous coronary intervention (PCI)...
July 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-anti-obesity-effects-in-diet-induced-obese-mice
#7
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
Glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans in addition to their potent anti-diabetic effects. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their anti-obesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog, exenatide, for the development of promising new anti-obesity drugs...
July 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28694087/a-mathematical-model-of-a-recombinant-humanized-anti-cocaine-monoclonal-antibody-s-effects-on-cocaine-pharmacokinetics-in-mice
#8
Hanna N Wetzel, Tongli Zhang, Andrew B Norman
AIMS: A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at an advanced stage of pre-clinical development as an immunotherapy for cocaine abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood. MAIN METHODS: A three-compartment model of the effects of h2E2 on cocaine's distribution was constructed. The model assumes that h2E2 binds to cocaine and that the h2E2-cocaine complex does not enter the brain but distributes between the central and peripheral compartments...
July 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28693837/-should-doses-of-antibiotics-be-adjusted
#9
V de Lastours
While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve therapeutic success and to limit the risks of the emergence of resistance. The optimization of antibiotic use and dosages must have a threefold objective: guarantee antibacterial efficacy, limit toxicities and limit emergence of resistant strains. However, with the increase in the number of multipathological patients, particularly those with renal or hepatic impairment, the increase in the number of patients with extreme weights and the use of antibiotics with narrower therapeutic margins, the adaptation of antibiotic dosages is becoming increasingly important...
July 7, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28685298/benchmarking-of-human-dose-prediction-for-inhaled-medicines-from-preclinical-in-vivo-data
#10
Therese Ericsson, Markus Fridén, Carina Kärrman-Mårdh, Ian Dainty, Ken Grime
PURPOSE: A scientifically robust prediction of human dose is important in determining whether to progress a candidate drug into clinical development. A particular challenge for inhaled medicines is that unbound drug concentrations at the pharmacological target site cannot be easily measured or predicted. In the absence of such data, alternative empirical methods can be useful. This work is a post hoc analysis based on preclinical in vivo pharmacokinetic/pharmacodynamic (PK/PD) data with the aim to evaluate such approaches and provide guidance on clinically effective dose prediction for inhaled medicines...
July 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28684371/pharmacokinetics-and-model-based-dosing-to-optimize-fludarabine-therapy-in-pediatric-hematopoietic-cell-transplant-recipients
#11
Vijay Ivaturi, Christopher C Dvorak, Danna Chan, Tao Liu, Morton J Cowan, Justin Wahlstrom, Melisa Stricherz, Cathryn Jennissen, Paul J Orchard, Jakub Tolar, Sung-Yun Pai, Liusheng Huang, Francesca Aweeka, Janel Long-Boyle
A prospective multi-center study was conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of fludarabine plasma (f-ara-a) and intracellular triphosphate (f-ara-ATP) in children undergoing hematopoietic cell transplantation (HCT) and receiving fludarabine with conditioning. Plasma and peripheral blood mononuclear cells (PBMCs) were collected over the course of therapy for quantitation of f-ara-a and f-ara-ATP. Nonlinear mixed effects modeling was used to develop the PK model, including identification of covariates impacting drug disposition...
July 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28677837/determination-of-tigecycline-in-human-plasma-by-lc-ms-ms-and-its-application-to-population-pharmacokinetics-study-in-chinese-patients-with-hospital-acquired-pneumonia
#12
Rong Shao, Xingang Li, Yangmin Hu, Jinliang Chen, Honggang Lou, Haibin Dai
A selective, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Tigecycline (TGC) in human plasma, using Tigecycline-d9 as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed-phase Waters Acquity UPLC® BEH-C18 column (2.1 mm × 50 mm ID, 1.7 μm) with a flow rate of 0.25 ml/min. The mobile phase consisted of water, containing 0...
July 5, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28677407/pharmacokinetic-pharmacodynamic-analysis-of-meropenem-for-the-treatment-of-nosocomial-pneumonia-in-intracerebral-hemorrhage-patients-by-monte-carlo-simulation
#13
Lingti Kong, Yan Tang, Xiaohua Zhang, Guoyu Lu, Meiling Yu, Qingping Shi, Xiaofei Wu
BACKGROUND: Nosocomial pneumonia (NP) is a frequent complication among patients with intracerebral hemorrhage (ICH). However, there are currently no pharmacokinetic (PK) and pharmacodynamic (PD) data to guide meropenem dosing in these patients. OBJECTIVE: To investigate the PK/PD properties of meropenem in these patients and whether the usual dosing regimens of meropenem (2-hour infusion, 1 g, every 8 hours) was suitable. METHODS: A total of 11 patients with a diagnosis of ICH complicated with NP were selected in the emergency internal medicine and treated with a 1-g/2-hours extended infusion model...
July 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28676080/pharmacokinetic-and-pharmacodynamic-modeling-of-oral-mitiglinide-on-glucose-lowering-in-healthy-chinese-volunteers
#14
Shijia Liu, Peidong Chen, Yang Zhao, Guoliang Dai, Bingting Sun, Yao Wang, Anwei Ding, Wenzheng Ju
BACKGROUND: Mitiglinide is a widely used agent for diabetic treatment. We established a pharmacokinetic-pharmacodynamic (PK-PD) model to illustrate the relationship between mitiglinide plasma concentration and its glucose lowering effects in healthy volunteers. METHODS: The volunteers participated in the test after the administration of a single dose of 10 mg mitiglinide. The drug concentration in Plasma and the values of glucose levels were determined by LC-MS/MS assay and hexokinase method...
July 4, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28666426/prediction-of-marbofloxacin-dosage-for-the-pig-pneumonia-pathogens-actinobacillus-pleuropneumoniae-and-pasteurella-multocida-by-pharmacokinetic-pharmacodynamic-modelling
#15
Lucy Dorey, Ludovic Pelligand, Peter Lees
BACKGROUND: Bacterial pneumonia in pigs occurs widely and requires antimicrobial therapy. It is commonly caused by the pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida. Marbofloxacin is an antimicrobial drug of the fluoroquinolone class, licensed for use against these organisms in the pig. In recent years there have been major developments in dosage schedule design, based on integration and modelling of pharmacokinetic (PK) and pharmacodynamic (PD) data, with the objective of optimising efficacy and minimising the emergence of resistance...
July 1, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28660432/human-microdosing-and-mice-xenograft-data-of-agm-130-applied-to-estimate-efficacious-doses-in-patients
#16
Wan-Su Park, Gab-Jin Park, Seunghoon Han, Sooho Ban, Moon-Young Park, San-Ho Kim, Seon-Myung Kim, Yong-Chul Kim, Hyung Sik Kim, Young G Shin, Dong-Seok Yim
PURPOSE: AGM-130 is a cyclin-dependent kinase inhibitor that exhibits dose-dependent efficacy in xenograft mouse models. During preclinical pharmacokinetic (PK) studies, mice and rats showed comparable PK parameters while dogs showed unusually high clearance (CL), which has made human PK prediction challenging. To address this discrepancy, we performed a human microdosing PK and developed a mouse PK/PD model in order to guide the first-in-human studies. METHODS: A microdose of AGM-130 was given via intravenous injection to healthy subjects...
June 28, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28655786/pharmacokinetics-and-pharmacodynamics-based-mathematical-modeling-identifies-an-optimal-protocol-for-metronomic-chemotherapy
#17
Joseph Ciccolini, Dominique Barbolosi, Christophe Meille, Aurelie Lombard, Cindy Serdjebi, Sarah Giacometti, Laetitia Padovani, Eddy Pasquier, Nicolas Andre
Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. In this study, we developed a pharmacokinetic/pharmacodynamic (PK/PD) mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy...
June 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28654314/cross-validation-of-a-glucose-insulin-glucagon-pharmacodynamics-model-for-simulation-using-data-from-patients-with-type-1-diabetes
#18
Sabrina Lyngbye Wendt, Ajenthen Ranjan, Jan Kloppenborg Møller, Signe Schmidt, Carsten Boye Knudsen, Jens Juul Holst, Sten Madsbad, Henrik Madsen, Kirsten Nørgaard, John Bagterp Jørgensen
BACKGROUND: Currently, no consensus exists on a model describing endogenous glucose production (EGP) as a function of glucagon concentrations. Reliable simulations to determine the glucagon dose preventing or treating hypoglycemia or to tune a dual-hormone artificial pancreas control algorithm need a validated glucoregulatory model including the effect of glucagon. METHODS: Eight type 1 diabetes (T1D) patients each received a subcutaneous (SC) bolus of insulin on four study days to induce mild hypoglycemia followed by a SC bolus of saline or 100, 200, or 300 µg of glucagon...
February 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28654297/eriodictyol-not-its-glucuronide-metabolites-attenuates-acetaminophen-induced-hepatotoxicity
#19
Ling Ye, Zhaoyu Wang, Yao Lan, Minghao Chen, Cailing Wen, Yanxian Hu, Zhong Qiu Liu
Acetaminophen (APAP) is one of the most commonly used oral analgesics and antipyretics, but hepatotoxicity including liver failure may occur after overdose. The therapeutic options for treating APAP hepatotoxicity are limited. Eriodictyol, a dietary flavonoid with anti-inflammatory and antioxidant properties, was used here to determine its protective effects against APAP-induced hepatotoxicity in mice. Various administration routes and pharmacokinetics-pharmacodynamics (PK-PD) analyses were used to determine these effects...
June 27, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28653244/%C3%AE-hydroxybutyric-acid-ghb-pharmacokinetics-and-pharmacodynamics-semi-mechanistic-and-physiologically-relevant-pk-pd-model
#20
Rutwij A Dave, Kristin E Follman, Marilyn E Morris
An overdose of γ-hydroxybutyric acid (GHB), a drug of abuse, results in fatality caused by severe respiratory depression. In this study, a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize monocarboxylate transporter 1 (MCT1)-mediated transport of GHB, as well as effects of GHB on respiration frequency, for IV doses of 200, 600, and 1500 mg/kg in rats. The proposed PK/PD model for GHB consists of nonlinear metabolism of GHB in the liver, MCT1-mediated renal reabsorption with physiologically relevant concurrent fluid reabsorption, MCT1-mediated uptake into the brain, and direct effects of binding of GHB to GABAB receptors on the PD parameter, respiration frequency...
June 26, 2017: AAPS Journal
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