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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
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
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
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...
March 10, 2017: European Journal of Drug Metabolism and Pharmacokinetics
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
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
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
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
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
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
L Pelligand, A Soubret, J N King, J Elliott, J P Mochel
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects...
November 2016: CPT: Pharmacometrics & Systems Pharmacology
Devender Kodati, Harish Kaushik Kotakonda, Narsimhareddy Yellu
BACKGROUND: Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1...
August 2017: European Journal of Drug Metabolism and Pharmacokinetics
Mélanie Prague, Daniel Commenges, Jon Michael Gran, Bruno Ledergerber, Jim Young, Hansjakob Furrer, Rodolphe Thiébaut
Highly active antiretroviral therapy (HAART) has proved efficient in increasing CD4 counts in many randomized clinical trials. Because randomized trials have some limitations (e.g., short duration, highly selected subjects), it is interesting to assess the effect of treatments using observational studies. This is challenging because treatment is started preferentially in subjects with severe conditions. This general problem had been treated using Marginal Structural Models (MSM) relying on the counterfactual formulation...
March 2017: Biometrics
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
Brianne E Phillips, Craig A Harms, Gregory A Lewbart, Lesanna L Lahner, Martin Haulena, Justin F Rosenberg, Mark G Papich
Sea urchin mass mortality events have been attributed to both infectious and noninfectious etiologies. Bacteria, including Vibrio spp. and Pseudoalteromonas spp., have been isolated during specific mortality events. Aquarium collection sea urchins are also subject to bacterial infections and could benefit from antimicrobial treatment, but pharmacokinetic studies have been lacking for this invertebrate group until recently. This study evaluated the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in the green sea urchin (Strongylocentrotus droebachiensis) after intracoelomic injection and medicated bath immersion administration...
March 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Husan-Ming Huang, Yi-Yu Shih, Chieh Lin
Mixed-effects models have been widely used in the analysis of longitudinal data. By presenting the parameters as a combination of fixed effects and random effects, mixed-effects models incorporating both within- and between-subject variations are capable of improving parameter estimation. In this work, we demonstrate the feasibility of using a non-linear mixed-effects (NLME) approach for generating parametric images from medical imaging data of a single study. By assuming that all voxels in the image are independent, we used simulation and animal data to evaluate whether NLME can improve the voxel-wise parameter estimation...
March 2016: NMR in Biomedicine
Brett Matzuka, Jason Chittenden, Jonathan Monteleone, Hien Tran
In nonlinear mixed effect (NLME) modeling, the intra-individual variability is a collection of errors due to assay sensitivity, dosing, sampling, as well as model misspecification. Utilizing stochastic differential equations (SDE) within the NLME framework allows the decoupling of the measurement errors from the model misspecification. This leads the SDE approach to be a novel tool for model refinement. Using Metformin clinical pharmacokinetic (PK) data, the process of model development through the use of SDEs in population PK modeling was done to study the dynamics of absorption rate...
February 2016: Journal of Pharmacokinetics and Pharmacodynamics
Markus Karlsson, David L I Janzén, Lucia Durrieu, Alejandro Colman-Lerner, Maria C Kjellsson, Gunnar Cedersund
BACKGROUND: Studies of cell-to-cell variation have in recent years grown in interest, due to improved bioanalytical techniques which facilitates determination of small changes with high uncertainty. Like much high-quality data, single-cell data is best analysed using a systems biology approach. The most common systems biology approach to single-cell data is the standard two-stage (STS) approach. In STS, data from each cell is analysed in a separate sub-problem, meaning that only data from the same cell is used to calculate the parameter values within that cell...
2015: BMC Systems Biology
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