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https://www.readbyqxmd.com/read/28821435/model-based-population-pk-pd-analysis-of-furosemide-for-bp-lowering-effect-a-comparative-study-in-primary-and-secondary-hypertension
#1
Mahendra Shukla, Moustafa M A Ibrahim, Moon Jain, Swati Jaiswal, Abhisheak Sharma, Kashif Hanif, Jawahar Lal
Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg(-1) multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using Emax model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models...
August 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28819873/similarities-and-differences-between-doxycycline-and-minocycline-clinical-and-antimicrobial-stewardship-considerations
#2
REVIEW
B A Cunha, J Baron, C B Cunha
Doxycycline and, to a lesser extent, minocycline, have been used for decades to treat various serious systemic infections, but many physicians remain unfamiliar with their spectrum, interpretation of susceptibility results, pharmacokinetic/pharmacodynamic (PK/PD) properties, optimal dosing regimens, and their activity against MRSA, VRE, and multidrug-resistant (MDR) Gram-negative bacilli, e.g., Acinetobacter sp. This article reviews the optimal use of doxycycline and minocycline to treat a variety of infections and when minocycline is preferred instead of doxycycline...
August 17, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28817201/exposure-response-modeling-and-power-analysis-of-components-of-acr-response-criteria-in-rheumatoid-arthritis-part-2-continuous-model
#3
Liang Li, Yi Zhang, Lian Ma, Ping Ji, Sarah Yim, Badrul A Chowdhury, Suresh Doddapaneni, Jiang Liu, Yaning Wang, Chandrahas Sahajwalla
Population pharmacokinetic/pharmacodynamic (PK/PD) models were developed to quantitate the exposure-response relationships using continuous longitudinal data on American College of Rheumatology (ACR) subcomponents, that is, tender-joint count (TJC), swollen-joint count (SJC), C-reactive protein, patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, and patient's assessment of physical function for 5 biologics approved for use in rheumatoid arthritis...
September 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28814243/a-pharmacokinetic-pharmacodynamic-model-of-tamoxifen-and-endoxifen-to-predict-their-distribution-and-effects-on-inhibition-of-tumor-growth
#4
Shengyue Yuan, Qingrong Sun, Yao Chen, Jun Liao
BACKGROUND: Tamoxifen is widely used in the therapy for breast cancer and has three major metabolites, N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen. Endoxifen has played a major role in the inhibition of tumor growth of breast cancer and the tumor growth is related to endoxifen concentration. OBJECTIVES: The aim of this study was to develop a pharmacokinetic-pharmacodynamic model to predict the distribution of tamoxifen and endoxifen quantitatively, and to discover the anti-tumor effect patterns of tamoxifen and endoxifen...
August 15, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#5
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28806566/volumetric-adsorptive-microsampling-liquid-chromatography-tandem-mass-spectrometry-assay-for-the-simultaneous-quantification-of-four-antibiotics-in-human-blood-method-development-validation-and-comparison-with-dried-blood-spot
#6
Sebastiano Barco, Elio Castagnola, Andrea Moscatelli, James Rudge, Gino Tripodi, Giuliana Cangemi
In this paper we show the development and validation of a volumetric absorptive microsampling (VAMS™)-LC-MS/MS method for the simultaneous quantification of four antibiotics: piperacillin-tazobactam, meropenem, linezolid and ceftazidime in 10μL human blood. The novel VAMS-LC-MS/MS method has been compared with a dried blood spot (DBS)-based method in terms of impact of hematocrit (HCT) on accuracy, reproducibility, recovery and matrix effect. Antibiotics were extracted from VAMS and DBS by protein precipitation with methanol after a re-hydration step at 37°C for 10min...
August 2, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28804722/comment-on-application-of-pk-pd-modeling-in-veterinary-field-dose-optimization-and-drug-resistance-prediction
#7
COMMENT
Anna Benini, Guido Francesco Fumagalli
No abstract text is available yet for this article.
2017: BioMed Research International
https://www.readbyqxmd.com/read/28803835/receptor-distribution-studies
#8
REVIEW
Renzo Carletti, Stefano Tacconi, Manolo Mugnaini, Philip Gerrard
Receptor distribution studies have played a key role in the characterization of receptor systems (e.g. GABAB, NMDA (GluNRs), and Neurokinin 1) and in generating hypotheses to exploit these systems as potential therapeutic targets. Distribution studies can provide important information on the potential role of candidate receptors in normal physiology/disease and alert for possible adverse effects of targeting the receptors. Moreover, they can provide valuable information relating to quantitative target engagement (e...
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28803333/low-dose-tolvaptan-pk-pd-comparison-of-patients-with-hyponatremia-due-to-syndrome-of-inappropriate-antidiuretic-hormone-secretion-to-healthy-adults
#9
Susan E Shoaf, Patricia Bricmont, Ann Dandurand
PURPOSE: Tolvaptan (TLV) is indicated to treat hyponatremia due to syndrome of inappropriate diuretic hormone (SIADH) in Europe. Treatment is to be initiated at 15 mg QD but post-approval reporting indicates increasing use of 7.5 mg as the starting dose. Physicians believe 7.5 mg is effective and has a lower incidence of overly rapid correction of serum sodium. METHODS: Single TLV doses of 3.75, 7.5, and 15 mg were administered to 14 healthy adults in a crossover design and to 29 subjects ≥18 years with SIADH and serum sodium between 120 and 133 mmol/L in a parallel-group design...
August 12, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28801120/establishment-of-valnemulin-susceptibility-breakpoint-against-clostridium-perfringens-in-rabbits
#10
Meng-Ting Tao, Yu-Feng Zhou, Jian Sun, Ya-Hong Liu, Xiao-Ping Liao
Susceptibility breakpoints provide fundamental information for rational administration of antibiotics. The present investigation reports the first valnemulin susceptibility breakpoint (MIC<0.25 μg/mL) against Clostridium perfringens infections in rabbits based on the wild-type cutoff (COWT) and the pharmacokinetics/pharmacodynamic (PK/PD) cutoff (COPD). The established susceptibility breakpoint of valnemulin might be useful in resistance surveillance of pleuromutilins and development of clinical breakpoints...
August 8, 2017: Anaerobe
https://www.readbyqxmd.com/read/28797065/a-systematic-review-of-the-pharmacokinetic-and-pharmacodynamic-interactions-of-herbal-medicine-with-warfarin
#11
Songie Choi, Dal-Seok Oh, Ui Min Jerng
OBJECTIVES: The aim of this study was to systematically review data regarding pharmacokinetic (PK)-pharmacodynamic (PD) parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin. METHODS: Three electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT)...
2017: PloS One
https://www.readbyqxmd.com/read/28780725/a-review-of-oral-cannabinoids-and-medical-marijuana-for-the-treatment-of-chemotherapy-induced-nausea-and-vomiting-a-focus-on-pharmacokinetic-variability-and-pharmacodynamics
#12
REVIEW
Melissa E Badowski
PURPOSE: Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV...
August 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28777819/infection-stage-adjusted-dose-of-beta-lactams-for-parsimonious-and-efficient-antibiotic-treatments-a-pasteurella-multocida-experimental-pneumonia-in-mice
#13
Maleck V Vasseur, Marlene Z Lacroix, Pierre-Louis Toutain, Alain Bousquet-Melou, Aude A Ferran
In this study, the impact of infection stage on clinically and microbiologically efficacious doses and on antibiotic consumption was assessed during a naturally evolving infectious disease, using an original mouse model of pulmonary infection produced by air-borne contamination. When Pasteurella multocida was administered as pathogenic agent to immunocompetent mice, 60% of the animals exhibited clinical symptoms of pneumonia 2 to 4 days after bacterial contamination of the lungs. Two beta-lactam antibiotics were evaluated: amoxicillin and cefquinome, a fourth generation cephalosporin developed for food animals...
2017: PloS One
https://www.readbyqxmd.com/read/28770387/data-to-decisions-creating-a-culture-of-model-driven-drug-discovery
#14
Frank K Brown, Farida Kopti, Charlie Zhenyu Chang, Scott A Johnson, Meir Glick, Chris L Waller
Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a "model-driven" culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a "Design Cycle" that makes use of all the data possible, internally and externally, to drive decision-making...
August 2, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28769004/pharmacokinetic-pharmacodynamic-analysis-for-doripenem-regimens-in-intensive-care-unit-patient
#15
Ryota Tanaka, Yuhki Sato, Koji Goto, Norihisa Yasuda, Yoshifumi Ohchi, Yosuke Suzuki, Tamio Ueno, Kentaro Ito, Tetsuya Kaneko, Shusaku Kurogi, Ko Nonoshita, Hiroki Itoh
Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28769002/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-luseogliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-japanese-patients-with-type-2-diabetes-mellitus
#16
Yoshishige Samukawa, Masaru Mutoh, Shi Chen, Nobuo Mizui
Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by promoting urinary glucose excretion (UGE). A clinical pharmacology study conducted in Japanese patients with T2DM confirmed dose-dependency of UGE with once-daily administration of luseogliflozin; however, the reason for sustained UGE after plasma luseogliflozin decreased was unclear. To elucidate the effect of inhibition rate constants, Kon and Koff, and to explain the sustained UGE, a pharmacokinetic-pharmacodynamic (PK-PD) model was built based on the mechanisms of glucose filtration in the glomerulus and reabsorption in the renal proximal tubule of kidney as well as the kinetics of competitive inhibition of SGLT1/2 and inhibition rate constants of SGLT2, by using UGE and plasma glucose levels and luseogliflozin concentrations...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28766381/development-and-validation-of-an-enzyme-linked-immunosorbent-assay-to-measure-free-eculizumab-concentration-in-serum
#17
Christophe Passot, Céline Desvignes, David Ternant, Theodora Bejan-Angoulvant, Anne-Claire Duveau, Philippe Gatault, Gilles Paintaud
AIM: Eculizumab is a monoclonal antibody toward C5 fraction of the complement system. It is approved to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. To perform pharmacokinetic studies and therapeutic drug monitoring, a validated assay is required. MATERIALS & METHODS: An indirect ELISA with recombinant human C5 sensitized microtiter plates were developed. RESULTS: The assay allows the measurement of free eculizumab concentration in human serum...
August 2, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28760708/experimental-design-and-modeling-approach-to-evaluate-efficacy-of-%C3%AE-lactam-%C3%AE-lactamase-inhibitor-combinations
#18
REVIEW
Sherwin K B Sy, Hartmut Derendorf
BACKGROUND: A β-lactamase inhibitor (BLI) confers susceptibility of β-lactamase-expressing multidrug resistant (MDR) organisms to the partnering β-lactam (BL). AIMS: To discuss the experimental design and modeling strategies for 2-drug combination, using ceftazidime- and aztreonam-avibactam combinations, as examples. SOURCES: The information came from several publications on avibactam in vitro time-kill studies and corresponding pharmacodynamic models...
July 28, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28759841/a-fast-and-sensitive-lc-ms-ms-method-for-the-quantification-of-fosfomycin-in-human-urine-and-plasma-using-one-sample-preparation-method-and-hilic-chromatography
#19
Rixt A Wijma, Soma Bahmany, E B Wilms, T van Gelder, Johan W Mouton, Birgit C P Koch
Fosfomycin is an old antibiotic that is increasingly prescribed because of emergence of the antibiotic resistance and the growing incidence of multi-drug resistant infections. Surprisingly, little is known about its pharmacokinetics (PK) and the pharmacodynamics (PD). Quantification of fosfomycin in both urine and plasma provides insight into the PK/PD characteristics of fosfomycin, which is crucial for the optimization of the therapy and the prevention of the emergence of resistance. An analytical method is therefore needed for the quantification of fosfomycin in both urine and plasma...
July 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28755409/a-first-in-human-pharmacodynamic-and-pharmacokinetic-study-of-a-fully-human-anti-glucagon-receptor-monoclonal-antibody-in-normal-healthy-volunteers
#20
Ana Kostic, Alexander T King, Feng Yang, Kuo-Chen Chan, George D Yancopoulos, Jesper Gromada, Joyce B Harp
AIMS: Glucagon receptor (GCGR) blockers are being investigated as potential therapeutics for type 1 and 2 diabetes. Here we report the safety, tolerability, pharmacokinetics [PK], and pharmacodynamics [PD] of REGN1193, a fully human glucagon receptor blocking monoclonal antibody from a first-in-human healthy volunteer randomized double blind trial. MATERIALS AND METHODS: Healthy men and women received single ascending doses of REGN1193 ranging from 0.05 mg/kg to 0...
July 28, 2017: Diabetes, Obesity & Metabolism
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