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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/28819627/pharmacokinetics-and-pharmacodynamics-evaluation-of-tramadol-in-thermoreversible-gels
#3
Juliana Zampoli Boava Papini, Cíntia Maria Saia Cereda, José Pedrazzoli Júnior, Silvana Aparecida Calafatti, Daniele Ribeiro de Araújo, Giovana Radomille Tofoli
We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) induced by new formulations of tramadol (TR) in thermoreversible gels. The poloxamer- (PL-) tramadol systems were prepared by direct dispersion of the drug in solutions with PL 407 and PL 188. The evaluated formulations were as follows: F1: TR 2% in aqueous solution and F2: PL 407 (20%) + PL 188 (10%) + TR 2%; F3: PL 407 (25%) + PL 188 (5%) + TR 2%; F4: PL 407 (20%) + TR 2%. New Zealand White rabbits were divided into four groups (n = 6) and treated by subcutaneous route with F1, F2, F3, or F4 (10 μg·kg(-1))...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28817223/single-dose-euglycemic-clamp-studies-demonstrating-pharmacokinetic-and-pharmacodynamic-similarity-between-mk-1293-insulin-glargine-and-originator-insulin-glargine-lantus-in-type-1-diabetes-and-healthy-subjects
#4
Michael Crutchlow, John S Palcza, Kate M Mostoller, Chantal D Mahon, April M Barbour, Michael C Marcos, Yang Xu, Elaine Watkins, Linda Morrow, Marcus Hompesch
AIMS: MK-1293 is an insulin glargine that has an identical amino acid sequence to that of Lantus, the originator insulin glargine. Two euglycemic clamp studies, one in subjects with Type 1 diabetes (T1D) and one in healthy subjects, were conducted to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) similarity between MK-1293 and Lantus commercially procured in both the European Union (EU-Lantus) and United States (US-Lantus). MATERIALS AND METHODS: Both studies were single-dose, randomized, double-blind, single-center, crossover studies with ≥7 days between dosing periods...
August 17, 2017: Diabetes, Obesity & Metabolism
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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/28803492/rifampin-vs-rifapentine-what-is-the-preferred-rifamycin-for-tuberculosis
#11
Omamah Alfarisi, Wael A Alghamdi, Mohammad H Al-Shaer, Kelly E Dooley, Charles A Peloquin
One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them...
August 14, 2017: Expert Review of Clinical 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
#12
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/28802779/pharmacological-aspects-of-closed-loop-insulin-delivery-for-type-1-diabetes
#13
REVIEW
Chukwuma Uduku, Nick Oliver
Insulin deficiency and impaired glucose homeostasis are hallmarks of type 1 diabetes. Since the discovery of insulin, pharmacological and clinical developments have endeavoured to replicate its endogenous pharmacokinetics (PK) and pharmacodynamics (PD). Closed loop insulin delivery systems operate as an artificial pancreas by making automated insulin dose adjustments based on real time continuous glucose monitoring. The increasing adoption of continuous insulin pump therapy and evolving technological advances have seen significant progress in the development of closed loop insulin delivery systems...
August 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28801120/establishment-of-valnemulin-susceptibility-breakpoint-against-clostridium-perfringens-in-rabbits
#14
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 9, 2017: Anaerobe
https://www.readbyqxmd.com/read/28797065/a-systematic-review-of-the-pharmacokinetic-and-pharmacodynamic-interactions-of-herbal-medicine-with-warfarin
#15
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/28782685/drug-target-residence-time-a-misleading-concept
#16
Rutger H A Folmer
Since the importance of drug target residence time was first highlighted more 10 years ago, slow binding kinetics has received much attention in the drug discovery literature, and indeed within pharmaceutical research. However, the residence concept as presented in most papers is supported by rather misleading simulations and arguments, and by examples where compounds are taken out of their pharmacokinetic context. Moreover, fast association is typically more desirable than slow, and advantages of long residence time, notably a potential disconnect between pharmacodynamics (PD) and pharmacokinetics (PK), would be partially or completely offset by slow on-rate...
August 3, 2017: Drug Discovery Today
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
#17
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
#18
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/28775208/a-multikinase-and-dna-pk-inhibitor-combination-immunomodulates-melanomas-suppresses-tumor-progression-and-enhances-immunotherapies
#19
Alexander K Tsai, Asra Y Khan, Christina E Worgo, Lucy L Wang, Yuanyuan Liang, Eduardo Davila
Combination therapies have the potential to improve outcomes in melanoma patients but have not yet been clinically efficacious. Here, we used high-throughput flow cytometry-based screening to identify and characterize candidate therapies that might synergize with and augment T-cell immunotherapy efficacy. Two lead therapies, regorafenib and NU7441, were selected based on their ability to alter a variety of immunomodulatory proteins, including CD55, CD73, CD155, programmed death-ligand 1 (PD-L1), nerve growth factor receptor (NGFR), and HLA class I in a heterogeneous panel of melanomas...
August 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28770387/data-to-decisions-creating-a-culture-of-model-driven-drug-discovery
#20
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
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