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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
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
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
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
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
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
Jeffrey R Harring, Shelley A Blozis
Nonlinear mixed-effects (NLME) models are used when analyzing continuous repeated measures data taken on each of a number of individuals where the focus is on characteristics of complex, nonlinear individual change. Challenges with fitting NLME models and interpreting analytic results have been well documented in the statistical literature. However, parameter estimates as well as fitted functions from NLME analyses in recent articles have been misinterpreted, suggesting the need for clarification of these issues before these misconceptions become fact...
November 2016: Multivariate Behavioral Research
Florent Baty, Christian Ritz, Arnoldus van Gestel, Martin Brutsche, Daniel Gerhard
BACKGROUND: The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake ([Formula: see text]O2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple [Formula: see text]O2 kinetics in both research and clinical practice so far...
2016: BMC Medical Research Methodology
William Adamiak, Amanda Thomas, Shivani Patel, Rick Gilmore
In adults, radial optic flow evokes stronger brain activity than laminar or rotational flow. Optic flow also evokes different activation patterns depending on motion speed (Fesi et al., 2014). This study examined whether the detection of optic flow in adult observers varies by pattern and speed in ways consistent with prior physiological evidence. Adult observers (n=10; 19.2-22.2 years, M=21.4) viewed two side-by-side, time varying (1.2 Hz coherent/incoherent cycle) annular shaped (18 deg outer/5 deg inner diameter) optic flow displays at a viewing distance of 60 cm...
2015: Journal of Vision
Raimonda Uosyte, Darren J Shaw, Danielle A Gunn-Moore, Eduardo Fraga-Manteiga, Tobias Schwarz
Turbinate destruction is an important diagnostic criterion in canine and feline nasal computed tomography (CT). However decreased turbinate visibility may also be caused by technical CT settings and nasal fluid. The purpose of this experimental, crossover study was to determine whether fluid reduces conspicuity of canine and feline nasal turbinates in CT and if so, whether CT settings can maximize conspicuity. Three canine and three feline cadaver heads were used. Nasal slabs were CT-scanned before and after submerging them in a water bath; using sequential, helical, and ultrahigh resolution modes; with images in low, medium, and high frequency image reconstruction kernels; and with application of additional posterior fossa optimization and high contrast enhancing filters...
September 2015: Veterinary Radiology & Ultrasound
Guangxiang Zhang, John J Chen
Linear mixed-effects model has been widely used in longitudinal data analyses. In practice, the fitting algorithm can fail to converge due to boundary issues of the estimated random-effects covariance matrix G, i.e., being near-singular, non-positive definite, or both. Current available algorithms are not computationally optimal because the condition number of matrix G is unnecessarily increased when the random-effects correlation estimate is not zero. We propose an adaptive fitting (AF) algorithm using an optimal linear transformation of the random-effects design matrix...
2013: Journal of Statistical Computation and Simulation
Jeffrey R Harring, Shelley A Blozis
Nonlinear mixed-effects (NLME) models remain popular among practitioners for analyzing continuous repeated measures data taken on each of a number of individuals when interest centers on characterizing individual-specific change. Within this framework, variation and correlation among the repeated measurements may be partitioned into interindividual variation and intraindividual variation components. The covariance structure of the residuals are, in many applications, consigned to be independent with homogeneous variances, [Formula: see text], not because it is believed that intraindividual variation adheres to this structure, but because many software programs that estimate parameters of such models are not well-equipped to handle other, possibly more realistic, patterns...
June 2014: Behavior Research Methods
Julia Müllauer, Claudia Kuntner, Martin Bauer, Jens P Bankstahl, Markus Müller, Rob A Voskuyl, Oliver Langer, Stina Syvänen
UNLABELLED: HASH(0x3cf2570) BACKGROUND: This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). METHODS: Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling...
2012: EJNMMI Research
T Z Albertini, S R Medeiros, R A A Torres, S S Zocchi, J W Oltjen, A B Strathe, D P D Lanna
The objective of this study was to evaluate methods to predict the secretion of milk and net energy and protein requirements of beef cows (Bos indicus and B. taurus) after approximately 1 mo postpartum using nonlinear mixed-effect modeling (NLME). Twenty Caracu × Nellore (CN) and 10 Nellore (NL) cows were inseminated to Red Angus bulls, and 10 Angus × Nellore (AN) were bred to Canchim bulls. Cows were evaluated from just after calving (25 ± 11 d) to weaning (220 d). Milk yield was estimated by weighing calves before and after suckling (WSW) and by machine milking (MM) methods at 25, 52, 80, 109, 136, 164, 193, and 220 ± 11 d of lactation...
November 2012: Journal of Animal Science
Xiaoyong Sun, Jun Li
BACKGROUND: Graphics play an important and unique role in population pharmacokinetic (PopPK) model building by exploring hidden structure among data before modeling, evaluating model fit, and validating results after modeling. RESULTS: The work described in this paper is about a new R package called PKreport, which is able to generate a collection of plots and statistics for testing model assumptions, visualizing data and diagnosing models. The metric system is utilized as the currency for communicating between data sets and the package to generate special-purpose plots...
2011: BMC Medical Informatics and Decision Making
Juan Francisco Hernández-Sierra, Facundo Ruíz, Juan Pablo Castanedo-Cázares, Vera Martinez-Ruiz, Peter Mandeville, Mauricio Pierdant-Pérez, Antonio Gordillo-Moscoso, Amaury de J Pozos-Guillén
Silver nanoparticles (NNPs), alone or in combination with the bioadhesive Gantrez S-97, have demonstrated their efficacy against Streptococcus mutans; however, it is not known if this combination changes the color of teeth. The aim of this work was to measure the color changes occurring after the use of a Gantrez-NNP combination on enamel tooth blocks. Two study groups were randomly formed: enamel blocks brushed with (a) the Gantrez-NNP combination and (b) conventional toothpaste, for 1 minute once daily for 4 weeks, then rinsed with distilled water and placed in thymol solution...
2010: Journal of Clinical Pediatric Dentistry
Clemens H M Kocken, Edmond J Remarque, Martin A Dubbeld, Sharon Wein, Annemarie van der Wel, R Joyce Verburgh, Henri J Vial, Alan W Thomas
Preclinical animal models informing antimalarial drug development are scarce. We have used asexual erythrocytic Plasmodium cynomolgi infections of rhesus macaques to model Plasmodium vivax during preclinical development of compounds targeting parasite phospholipid synthesis. Using this malaria model, we accumulated data confirming highly reproducible infection patterns, with self-curing parasite peaks reproducibly preceding recrudescence peaks. We applied nonlinear mixed-effect (NLME) models, estimating treatment effects in three drug studies: G25 (injected) and the bisthiazolium prodrugs TE4gt and TE3 (oral)...
February 2009: Antimicrobial Agents and Chemotherapy
W Hou, H Li, B Zhang, M Huang, R Wu
Functional mapping has emerged as a next-generation statistical tool for mapping quantitative trait loci (QTL) that affect complex dynamic traits. In this article, we incorporated the idea of nonlinear mixed-effect (NLME) models into the mixture-based framework of functional mapping, aimed to generalize the spectrum of applications for functional mapping. NLME-based functional mapping, implemented with the linearization algorithm based on the first-order Taylor expansion, can provide reasonable estimates of QTL genotypic-specific curve parameters (fixed effect) and the between-individual variation of these parameters (random effect)...
October 2008: Heredity
Xavière Panhard, Adeline Samson
This article focuses on parameter estimation of multilevel nonlinear mixed-effects models (MNLMEMs). These models are used to analyze data presenting multiple hierarchical levels of grouping (cluster data, clinical trials with several observation periods, ...). The variability of the individual parameters of the regression function is thus decomposed as a between-subject variability and higher levels of variability (e.g. within-subject variability). We propose maximum likelihood estimates of parameters of those MNLMEMs with 2 levels of random effects, using an extension of the stochastic approximation version of expectation-maximization (SAEM)-Monte Carlo Markov chain algorithm...
January 2009: Biostatistics
Stig B Mortensen, Søren Klim, Bernd Dammann, Niels R Kristensen, Henrik Madsen, Rune V Overgaard
The non-linear mixed-effects model based on stochastic differential equations (SDEs) provides an attractive residual error model, that is able to handle serially correlated residuals typically arising from structural mis-specification of the true underlying model. The use of SDEs also opens up for new tools for model development and easily allows for tracking of unknown inputs and parameters over time. An algorithm for maximum likelihood estimation of the model has earlier been proposed, and the present paper presents the first general implementation of this algorithm...
October 2007: Journal of Pharmacokinetics and Pharmacodynamics
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