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https://www.readbyqxmd.com/read/29435161/nonlinear-mixed-effects-dose-response-modeling-in-high-throughput-drug-screens-application-to-melanoma-cell-line-analysis
#1
Kuan-Fu Ding, Emanuel F Petricoin, Darren Finlay, Hongwei Yin, William P D Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar Sekulic, Patricia M LoRusso, Kristiina Vuori, Jeffrey M Trent, Nicholas J Schork
Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC50). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29368268/a-distributed-delay-approach-for-modeling-delayed-outcomes-in-pharmacokinetics-and-pharmacodynamics-studies
#2
Shuhua Hu, Michael Dunlavey, Serge Guzy, Nathan Teuscher
A distributed delay approach was proposed in this paper to model delayed outcomes in pharmacokinetics and pharmacodynamics studies. This approach was shown to be general enough to incorporate a wide array of pharmacokinetic and pharmacodynamic models as special cases including transit compartment models, effect compartment models, typical absorption models (either zero-order or first-order absorption), and a number of atypical (or irregular) absorption models (e.g., parallel first-order, mixed first-order and zero-order, inverse Gaussian, and Weibull absorption models)...
January 24, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29285245/a-population-pharmacokinetic-model-for-individualised-dosage-regimens-of-vancomycin-in-chinese-neonates-and-young-infants
#3
Lin Song, Cui-Yao He, Nan-Ge Yin, Fang Liu, Yun-Tao Jia, Yao Liu
Population pharmacokinetic (PPK) modelling is an easy and impartment method for estimating drug concentration for use inindividualized therapy, especially for young patients and to help protect drug-induced diseases. The purpose of this study was to develop a PPK model for effective dosing of vancomycin in Chinese neonates and young infants. The PPK modelling tool Phoenix® NLME™ was use to assess demographic and routine clinical pharmacokinetic (PK) data retrospectively collected for patients admitted to Children's Hospital of Chongqing Medical University between 2011 and 2016...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226975/mathematical-modeling-and-simulation-in-animal-health-part-iii-using-nonlinear-mixed-effects-to-characterize-and-quantify-variability-in-drug-pharmacokinetics
#4
REVIEW
C Bon, P L Toutain, D Concordet, R Gehring, T Martin-Jimenez, J Smith, L Pelligand, M Martinez, T Whittem, J E Riviere, J P Mochel
A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between-patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food-producing animals...
December 11, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29119381/comparison-of-tenofovir-plasma-and-tissue-exposure-using-a-population-pharmacokinetic-model-and-bootstrap-a-simulation-study-from-observed-data
#5
Jon W Collins, J Heyward Hull, Julie B Dumond
Sparse tissue sampling with intensive plasma sampling creates a unique data analysis problem in determining drug exposure in clinically relevant tissues. Tissue exposure may govern drug efficacy, as many drugs exert their actions in tissues. We compared tissue area-under-the-curve (AUC) generated from bootstrapped noncompartmental analysis (NCA) methods and compartmental nonlinear mixed effect (NLME) modeling. A model of observed data after single-dose tenofovir disoproxil fumarate was used to simulate plasma and tissue concentrations for two destructive tissue sampling schemes...
December 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29112289/pharmacokinetics-of-intravenous-lithium-chloride-and-assessment-of-agreement-between-two-methods-of-lithium-concentration-measurement-in-the-horse
#6
L M Martin, A D Bukoski, D D Whelchel, T J Evans, C E Wiedmeyer, S J Black, P J Johnson
BACKGROUND: Pharmacokinetics of lithium chloride (LiCl) administered as a bolus, once intravenously (i.v.) have not been determined in horses. There is no point-of-care test to measure lithium (Li(+) ) concentrations in horses in order to monitor therapeutic levels and avoid toxicity. OBJECTIVES: Determine the pharmacokinetics of LiCl in healthy adult horses and compare agreement between two methods of measurement of plasma Li(+) concentration: spectrophotometric enzymatic assay (SEA) and inductively coupled plasma mass spectrometry (ICP-MS)...
November 7, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/29080062/joint-model-based-clustering-of-nonlinear-longitudinal-trajectories-and-associated-time-to-event-data-analysis-linked-by-latent-class-membership-with-application-to-aids-clinical-studies
#7
Yangxin Huang, Xiaosun Lu, Jiaqing Chen, Juan Liang, Miriam Zangmeister
Longitudinal and time-to-event data are often observed together. Finite mixture models are currently used to analyze nonlinear heterogeneous longitudinal data, which, by releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, can cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, and be associated with clinically important time-to-event data. This article develops a joint modeling approach to a finite mixture of NLME models for longitudinal data and proportional hazard Cox model for time-to-event data, linked by individual latent class indicators, under a Bayesian framework...
October 27, 2017: Lifetime Data Analysis
https://www.readbyqxmd.com/read/28947805/comparative-population-pharmacokinetics-and-absolute-oral-bioavailability-of-cox-2-selective-inhibitors-celecoxib-mavacoxib-and-meloxicam-in-cockatiels-nymphicus-hollandicus
#8
Laura Dhondt, Mathias Devreese, Siska Croubels, Siegrid De Baere, Roel Haesendonck, Tess Goessens, Ronette Gehring, Patrick De Backer, Gunther Antonissen
Selective COX-2 inhibitors are non-steroidal anti-inflammatory drugs which directly target cyclooxygenase-2 (COX-2), an enzyme mainly responsible for induction of inflammation, pyresis and pain. Although commonly used in avian medicine, limited pharmacokinetic (PK) data in domestic and companion birds are available. In this study, PK parameters and absolute oral bioavailability expressed as percentage (F%) of celecoxib (10 mg/kg BW), mavacoxib (4 mg/kg BW) and meloxicam (1 mg/kg BW) were determined following single oral (PO) and intravenous (IV) administration to cockatiels (Nymphicus hollandicus)...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28937535/validation-of-a-commercial-assay-and-decision-support-tool-for-routine-paclitaxel-therapeutic-drug-monitoring-tdm
#9
Markus Joerger, Stefanie Kraff, Ulrich Jaehde, Ralf A Hilger, Jodi B Courtney, Daniel J Cline, Sonali Jog, Irina Baburina, M Craig Miller, Salvatore J Salamone
BACKGROUND: The value of therapeutic drug monitoring (TDM) for paclitaxel (PTX) was recently demonstrated in the largest TDM trial ever conducted in oncology. The trial demonstrated significant reduction in neuropathy when using TDM. Dose adjustment for PTX was based on time above a threshold concentration (Tc>0.05). Tc>0.05 must be calculated with a pharmacokinetic model and complex nonlinear mixed-effects software. The use of the software and chromatographic methods to measure PTX requires specialized expertise...
December 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28676080/pharmacokinetic-and-pharmacodynamic-modeling-of-oral-mitiglinide-on-glucose-lowering-in-healthy-chinese-volunteers
#10
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/28341596/application-of-an-nlme-stochastic-deconvolution-approach-to-level-a-ivivc-modeling
#11
Maziar Kakhi, Sandra Suarez-Sharp, Terry Shepard, Jason Chittenden
Stochastic deconvolution is a parameter estimation method that calculates drug absorption using a nonlinear mixed-effects model in which the random effects associated with absorption represent a Wiener process. The present work compares (1) stochastic deconvolution and (2) numerical deconvolution, using clinical pharmacokinetic (PK) data generated for an in vitro-in vivo correlation (IVIVC) study of extended release formulations of a Biopharmaceutics Classification System class III drug substance. The preliminary analysis found that numerical and stochastic deconvolution yielded superimposable fraction absorbed (Fabs) versus time profiles when supplied with exactly the same externally determined unit impulse response parameters...
March 22, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28340405/population-pharmacokinetic-modeling-of-furosemide-in-patients-with-hypertension-and-fluid-overload-conditions
#12
Devender Kodati, Narsimhareddy Yellu
BACKGROUND: Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. OBJECTIVE: The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. METHODS: A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28283988/nicotine-population-pharmacokinetics-in-healthy-adult-smokers-a-retrospective-analysis
#13
Mathilde Marchand, Patrick Brossard, Henri Merdjan, Nicola Lama, Rolf Weitkunat, Frank Lüdicke
BACKGROUND AND OBJECTIVE: Characterizing nicotine pharmacokinetics is challenging in the presence of background exposure. We performed a combined retrospective population pharmacokinetic analysis of 8 trials, including exposure to Tobacco Heating System and cigarettes (both inhaled), nicotine nasal spray and oral nicotine gum. METHOD: Data from 4 single product use trials were used to develop a population pharmacokinetic model with Phoenix(®) NLME™ and to derive exposure parameters...
December 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28254068/phxnlme-an-r-package-that-facilitates-pharmacometric-workflow-of-phoenix-nlme-analyses
#14
Chay Ngee Lim, Shuang Liang, Kevin Feng, Jason Chittenden, Ana Henry, Samer Mouksassi, Angela K Birnbaum
BACKGROUND AND OBJECTIVE: Pharmacometric analyses are integral components of the drug development process, and Phoenix NLME is one of the popular software used to conduct such analyses. To address current limitations with model diagnostic graphics and efficiency of the workflow for this software, we developed an R package, Phxnlme, to facilitate its workflow and provide improved graphical diagnostics. METHODS: Phxnlme was designed to provide functionality for the major tasks that are usually performed in pharmacometric analyses (i...
March 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28154789/cyp2b6-genotype-guided-dosing-of-propofol-anesthesia-in-the-elderly-based-on-nonparametric-population-pharmacokinetic-modeling-and-simulations
#15
Andy R Eugene
OBJECTIVE: The primary aim of this article is to test the hypothesis that nonparametric pharmacometric modeling will accurately identify CYP2B6 genotype subgroups based on data from a study that reported results based on parametric pharmacokinetics (PK). METHODS: Propofol concentration-time data were originally reported in the Kansaku et al. 2011 publication. Nonparametric Nonlinear Mixed Effects Modeling (NLME) was conducted using the PMETRICS R package while population pharmacokinetic model parameters were estimated using a FORTRAN compiler...
2017: International Journal of Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28048150/th-cd-207b-04-is-ttf-a-true-representation-of-the-sharpness-property-of-a-non-linear-ct-system
#16
M Robins, J Solomon, E Samei
PURPOSE: To investigate if the task-transfer-function (TTF) accurately models the transfer properties of a CT system for lung nodule imaging. METHODS: An anthropomorphic lung phantom was imaged using a standard chest protocol on a clinical CT scanner with and without 24 physically inserted synthetic lesions (nominal diameter: 8 - 10 mm). Images were reconstructed using FBP and iterative algorithm (SAFIRE, Siemens Healthcare). 3D TTF was measured using an established technique...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27995128/intravenous-topiramate-pharmacokinetics-in-dogs-with-naturally-occurring-epilepsy
#17
Irene Vuu, Lisa D Coles, Patricia Maglalang, Ilo E Leppik, Greg Worrell, Daniel Crepeau, Usha Mishra, James C Cloyd, Edward E Patterson
RATIONALE: Barriers to developing treatments for human status epilepticus include the inadequacy of experimental animal models. In contrast, naturally occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy and evaluate its effect on intracranial electroencephalographic (iEEG) features...
2016: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/27936356/bayesian-quantile-regression-for-nonlinear-mixed-effects-joint-models-for-longitudinal-data-in-the-presence-of-mismeasured-covariate-errors
#18
Yangxin Huang, Jiaqing Chen, Huahai Qiu
Quantile regression (QR) models have recently received increasing attention in longitudinal studies where measurements of the same individuals are taken repeatedly over time. When continuous (longitudinal) responses follow a distribution that is quite different from a normal distribution, usual mean regression (MR)-based linear models may fail to produce efficient estimators, whereas QR-based linear models may perform satisfactorily. To the best of our knowledge, there have been very few studies on QR-based nonlinear models for longitudinal data in comparison to MR-based nonlinear models...
December 9, 2016: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/27927703/pharmacokinetics-and-pharmacodynamics-of-oral-mecamylamine-development-of-a-nicotinic-acetylcholine-receptor-antagonist-cognitive-challenge-test-using-modelling-and-simulation
#19
Ricardo Alvarez-Jimenez, Anne Catrien Baakman, Jasper Stevens, Sebastiaan C Goulooze, Ellen P Hart, Robert Rissmann, Joop Ma van Gerven, Geert Jan Groeneveld
A pharmacologic challenge model with a nicotinic antagonist could be an important tool not only to understand the complex role of the nicotinic cholinergic system in cognition, but also to develop novel compounds acting on the nicotinic acetylcholine receptor. The objective was to develop a pharmacokinetic-pharmacodynamic (PKPD) model using nonlinear mixed effects (NLME) methods to quantitate the pharmacokinetics of three oral mecamylamine doses (10, 20 and 30 mg) and correlate the plasma concentrations to the pharmacodynamic effects on a cognitive and neurophysiologic battery of tests in healthy subjects...
December 7, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27863483/estimation-of-tulathromycin-depletion-in-plasma-and-milk-after-subcutaneous-injection-in-lactating-goats-using-a-nonlinear-mixed-effects-pharmacokinetic-modeling-approach
#20
Zhoumeng Lin, Matthew Cuneo, Joan D Rowe, Mengjie Li, Lisa A Tell, Shayna Allison, Jan Carlson, Jim E Riviere, Ronette Gehring
BACKGROUND: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i...
November 18, 2016: BMC Veterinary Research
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