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"Allometric scaling"

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https://www.readbyqxmd.com/read/27903219/prediction-of-plasma-concentration-time-profiles-of-drugs-in-humans-from-animals-following-oral-administration-an-allometric-approach
#1
Iftekhar Mahmood
BACKGROUND: Allometric scaling is regularly used for the prediction of human pharmacokinetic (PK) parameters from animal PK studies. The predicted human PK parameters can also be used for the prediction of plasma concentration-time profiles in humans. OBJECTIVES: The main objective of this work is to predict human concentration-time profiles of drugs (one-compartment model) following oral administration using animal oral pharmacokinetic parameters. METHODS: Six drugs from the literature were chosen that were described by one-compartment model in both humans and animals following oral administration...
November 21, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27902691/do-vascular-networks-branch-optimally-or-randomly-across-spatial-scales
#2
Elif Tekin, David Hunt, Mitchell G Newberry, Van M Savage
Modern models that derive allometric relationships between metabolic rate and body mass are based on the architectural design of the cardiovascular system and presume sibling vessels are symmetric in terms of radius, length, flow rate, and pressure. Here, we study the cardiovascular structure of the human head and torso and of a mouse lung based on three-dimensional images processed via our software Angicart. In contrast to modern allometric theories, we find systematic patterns of asymmetry in vascular branching, potentially explaining previously documented mismatches between predictions (power-law or concave curvature) and observed empirical data (convex curvature) for the allometric scaling of metabolic rate...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27892765/comparison-of-predictability-for-human-pharmacokinetics-parameters-among-monkeys-rats-and-chimeric-mice-with-humanised-liver
#3
Maki Miyamoto, Shinji Iwasaki, Ikumi Chisaki, Sayaka Nakagawa, Nobuyuki Amano, Hideki Hirabayashi
The aim of the present study was to evaluate the usefulness of chimeric mice with humanised liver (PXB mice) for the prediction of clearance (CLt) and volume of distribution at steady state (Vdss), in comparison with monkeys, which have been reported as a reliable model for human pharmacokinetics (PK) prediction, and with rats, as a conventional PK model. CLt and Vdss values in PXB mice, monkeys, and rats were determined following intravenous administration of 30 compounds known to be mainly eliminated in humans via the hepatic metabolism by various drug-metabolising enzymes...
November 28, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27828977/dinosaur-metabolism-and-the-allometry-of-maximum-growth-rate
#4
Nathan P Myhrvold
The allometry of maximum somatic growth rate has been used in prior studies to classify the metabolic state of both extant vertebrates and dinosaurs. The most recent such studies are reviewed, and their data is reanalyzed. The results of allometric regressions on growth rate are shown to depend on the choice of independent variable; the typical choice used in prior studies introduces a geometric shear transformation that exaggerates the statistical power of the regressions. The maximum growth rates of extant groups are found to have a great deal of overlap, including between groups with endothermic and ectothermic metabolism...
2016: PloS One
https://www.readbyqxmd.com/read/27799204/population-pharmacokinetic-modeling-to-estimate-the-contribution-of-genetic-and-non-genetic-factors-of-efavirenz-disposition
#5
Jason D Robarge, Ingrid F Metzger, Jessica Lu, Nancy Thong, Todd C Skaar, Zeruesenay Desta, Robert R Bies
Efavirenz pharmacokinetics is characterized by large between-subject variability, which determines both therapeutic response and adverse effects. Some of the variability in efavirenz pharmacokinetics has been attributed to genetic variability in cytochrome P450 genes that alter efavirenz metabolism, such as CYP2B6 and CYP2A6 While the effects of additional patient factors have been studied, such as sex, weight, and body mass index, the extent to which they contribute to variability in efavirenz exposure is inconsistently reported...
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27771399/noninvasive-ct-derived-ffr-based-on%C3%A2-structural-and%C3%A2-fluid-analysis-a-comparison-with-invasive-ffr-for-detection-of-functionally-significant-stenosis
#6
Brian S Ko, James D Cameron, Ravi K Munnur, Dennis T L Wong, Yasuko Fujisawa, Takuya Sakaguchi, Kenji Hirohata, Jacqui Hislop-Jambrich, Shinichiro Fujimoto, Kazuhisa Takamura, Marcus Crossett, Michael Leung, Ahilan Kuganesan, Yuvaraj Malaiapan, Arthur Nasis, John Troupis, Ian T Meredith, Sujith K Seneviratne
OBJECTIVES: This study describes the feasibility and accuracy of a novel computed tomography (CT) fractional flow reserve (FFR) technique based on alternative boundary conditions. BACKGROUND: Techniques used to compute FFR based on images acquired from coronary computed tomography angiography (CTA) are described. Boundary conditions were typically determined by allometric scaling laws and assumptions regarding microvascular resistance. Alternatively, boundary conditions can be derived from the structural deformation of coronary lumen and aorta, although its accuracy remains unknown...
October 14, 2016: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27763679/theory-based-pkpd-of-s-and-r-warfarin-and-effects-on-inr-influence-of-body-size-composition-and-genotype-in-cardiac-surgery-patients
#7
Ling Xue, Nick Holford, Xiao-Liang Ding, Zhen-Ya Shen, Chen-Rong Huang, Hua Zhang, Jing-Jing Zhang, Zhe-Ning Guo, Cheng Xie, Ling Zhou, Zhi-Yao Chen, Lin-Sheng Liu, Li-Yan Miao
AIMS: The aims of this study are to apply a theory based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin. METHODS: Clinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population pharmacokinetic parameter with data method was used to describe the international normalized ratio (INR) time course...
October 20, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27741055/reference-curves-for-field-tests-of-musculoskeletal-fitness-in-u-s-children-and-adolescents-the-2012-nhanes-national-youth-fitness-survey
#8
Kelly R Laurson, Pedro F Saint-Maurice, Gregory J Welk, Joey C Eisenmann
The purpose of the study was to describe current levels of musculoskeletal fitness (MSF) in U.S. youth by creating nationally representative age- and sex-specific growth curves for handgrip strength (including relative and allometrically scaled handgrip), modified pull-ups, and the plank test. Participants in the National Youth Fitness Survey (n = 1453) were tested on MSF, aerobic capacity (via submaximal treadmill test), and body composition (body mass index [BMI], waist circumference, and skinfolds). Using LMS regression, age- and sex-specific smoothed percentile curves of MSF were created and existing percentiles were used to assign age- and sex-specific z-scores for aerobic capacity and body composition...
October 6, 2016: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/27705784/hierarchical-size-scaling-during-multicellular-growth-and-development
#9
Sravanti Uppaluri, Stephanie C Weber, Clifford P Brangwynne
Multicellular organisms must regulate their growth across the diverse length scales of biological organization, but how this growth is controlled from organelle to body, while coordinating interdependent functions at each scale, remains poorly understood. We utilized the C. elegans worm intestine as a model system to identify distinct allometric scaling laws, revealing that the growth of individual structures is differentially regulated during development. We show that the volume of the nucleolus, a subcellular organelle, is directly proportional (isometric) to cell size during larval development...
October 4, 2016: Cell Reports
https://www.readbyqxmd.com/read/27704554/prediction-of-clearance-in-neonates-and-infants-%C3%A2-3-months-of-age-for-drugs-that-are-glucuronidated-a-comparative-study-between-allometric-scaling-and-physiologically-based-pharmacokinetic-modeling
#10
Iftekhar Mahmood, Tasneem Ahmad, Najia Mansoor, S M Sharib
The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (≤ 3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs. A PBPK model was developed using the physicochemical, biopharmaceutical, and metabolic properties together with known pediatric physiology and enzymatic ontogeny...
October 4, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27686596/allometric-scaling-of-electrical-excitation-and-propagation-in-the-mammalian-heart
#11
Guillaume Bassil, Manuel Zarzoso, Sami F Noujaim
Variations in body mass impose constraints on the structure and function of mammalian species, including those of the cardiovascular system. Numerous biological processes, including cardiovascular parameters, have been shown to scale with body mass (BM) according to the law of allometric scaling: Y = Y =a∙BM(b) (Y, biological process; a, normalization constant; b, scaling exponent, which in many instances is a multiple of ¼). These parameters include heart and breathing rates, intervals and subintervals of the electrocardiogram (ECG), action potential duration (APD), metabolic rate, and temporal properties of ventricular fibrillation...
September 26, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27669442/arterial-stiffness-is-reduced-regardless-of-resistance-training-load-in-young-men
#12
Jason S Au, Sara Y Oikawa, Robert W Morton, Maureen J MacDonald, Stuart M Phillips
PURPOSE: Discrepancies regarding the impact of resistance exercise training (RET) on arterial stiffness have led to uncertainty regarding the impact of RET on cardiovascular health. Confounding our understanding in this area are the roles of: load (heavier vs lighter), participant cardiovascular health, and the method of arterial stiffness assessment. We aimed to investigate the effects of a heavier versus a lighter load resistance training protocol on both central and local arterial stiffness in previously-trained young men...
September 23, 2016: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/27667689/right-ventricular-involvement-in-feline-hypertrophic-cardiomyopathy
#13
K E Schober, S I Savino, V Yildiz
OBJECTIVES: To evaluate right ventricular (RV) wall thickness and chamber dimensions in cats with hypertrophic cardiomyopathy (HCM). ANIMALS: One hundred fifty-one healthy control cats and 200 cats with HCM. METHODS: Retrospective, observational, clinical cohort study. Two-dimensional echocardiograms from all cats were analyzed. Right atrial diameter, RV free wall thickness, and RV chamber diameter were quantified using multiple imaging views...
September 22, 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/27649629/allometry-is-a-reasonable-choice-in-pediatric-drug-development
#14
Tao Liu, Parima Ghafoori, Jogarao V S Gobburu
Pharmacokinetics (PK) plays a key role in bridging drug efficacy and safety from adults to pediatrics. The principal purpose of projecting dosing in pediatrics is to guide trial design, not to waive the study per se. This research was designed to evaluate whether the allometric scaling (AS) approach is a satisfactory method to design PK study in pediatric patients 2 years and older. We systematically evaluated drugs that had pediatrics label information updated from 1998 to 2015. Only intravenous (IV) or oral administration drugs with available PK information in both pediatrics and adults from FDA approved labels were included...
September 21, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27637171/use-of-a-target-mediated-drug-disposition-model-to-predict-the-human-pharmacokinetics-and-target-occupancy-of-gc1118-an-anti-epidermal-growth-factor-receptor-antibody
#15
Wan-Su Park, Seunghoon Han, Jongtae Lee, Taegon Hong, Jonghwa Won, Yangmi Lim, Kyuhyun Lee, Han Yeul Byun, Dong-Seok Yim
GC1118 is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non-compartmental analysis and a target-mediated drug disposition (TMDD) model following intravenous infusion (3-25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis...
September 16, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27633491/the-1-500-m-rowing-performance-is-highly-dependent-on-modified-wingate-anaerobic-test-performance-in-national-level-adolescent-rowers
#16
Hugo Maciejewski, Abderrahmane Rahmani, Frédéric Chorin, Julien Lardy, Caroline Giroux, Sébastien Ratel
PURPOSE: The aim of the current study was to determine whether the anaerobic performance assessed by a modified Wingate test could account for the 1,500-m rowing ergometer performance in young competitive rowers. METHODS: Fourteen national-level adolescent rowers performed on a rowing ergometer i) a 30-s allout exercise (i.e., modified Wingate test) and ii) a 1,500-m all-out exercise (i.e., rowing performance). For each of these two exercises, the mean power output was considered as the main performance criterion (PWIN and P1500, respectively)...
November 2016: Pediatric Exercise Science
https://www.readbyqxmd.com/read/27632141/curios-relationship-revealed-by-looking-at-long-term-data-sets-the-geometry-and-allometric-scaling-of-diel-xylem-sap-flux-in-tropical-trees
#17
Norbert Kunert
Daily xylem sap flux values (daily Js) and maximum xylem sap flux values (max Js) from 125 tropical trees from different study sites in the Neotropics were compared. A cross species and study site relationship was found between daily and maximum values. The relationship can be expressed as daily Js=6.5x max Js. The geometrical relationship between the maximum xylem sap flux of a given day is thus defining the daily xylem sap flux rates. Assuming a bell-shaped diurnal sap flux course and a relatively constant day length the maximum xylem sap flux is the only possible changing variable to define daily fluxes...
September 2, 2016: Journal of Plant Physiology
https://www.readbyqxmd.com/read/27632065/pharmacokinetic-modeling-of-paracetamol-uptake-and-clearance-in-zebrafish-larvae-expanding-the-allometric-scale-in-vertebrates-with-five-orders-of-magnitude
#18
Vasudev Kantae, Elke H J Krekels, Anita Ordas, Oskar González, Rob C van Wijk, Amy C Harms, Peter I Racz, Piet H van der Graaf, Herman P Spaink, Thomas Hankemeier
Zebrafish larvae (Danio rerio) are increasingly used to translate findings regarding drug efficacy and safety from in vitro-based assays to vertebrate species, including humans. However, the limited understanding of drug exposure in this species hampers its implementation in translational research. Using paracetamol as a paradigm compound, we present a novel method to characterize pharmacokinetic processes in zebrafish larvae, by combining sensitive bioanalytical methods and nonlinear mixed effects modeling...
December 2016: Zebrafish
https://www.readbyqxmd.com/read/27632013/erratum-to-effects-of-body-chemical-components-on-the-allometric-scaling-of-the-resting-metabolic-rate-in-four-species-of-cyprinids
#19
Ge Li, Hang Xie, Dingcong He, Yiping Luo
No abstract text is available yet for this article.
September 8, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/27618527/the-relationship-between-maximal-strength-and-reactive-strength
#20
Kris Beattie, Brian P Carson, Mark Lyons, Ian C Kenny
Maximum- and reactive-strength qualities both have important roles in athletic movements and sporting performance. Very little research has investigated the relationship between maximum-strength and reactive-strength. The aim of this study was to investigate the relationship between maximum-strength (isometric mid-thigh pull peak force; IMTP PF) and reactive-strength (drop-jump reactive-strength index; DJ-RSI) variables at 0.3 m, 0.4 m, 0.5 m and 0.6 m box heights. A secondary aim investigated the between- and within-group differences in reactive-strength characteristics between relatively 'strong' and 'weak' athletes...
September 6, 2016: International Journal of Sports Physiology and Performance
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