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"Allometric scaling"

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https://www.readbyqxmd.com/read/28808917/development-of-a-translational-physiologically-based-pharmacokinetic-model-for-antibody-drug-conjugates-a-case-study-with-t-dm1
#1
Antari Khot, Jay Tibbitts, Dan Rock, Dhaval K Shah
Systems pharmacokinetic (PK) models that can characterize and predict whole body disposition of antibody-drug conjugates (ADCs) are needed to support (i) development of reliable exposure-response relationships for ADCs and (ii) selection of ADC targets with optimal tumor and tissue expression profiles. Towards this goal, we have developed a translational physiologically based PK (PBPK) model for ADCs, using T-DM1 as a tool compound. The preclinical PBPK model was developed using rat data. Biodistribution of DM1 in rats was used to develop the small molecule PBPK model, and the PK of conjugated trastuzumab (i...
August 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28804951/allometric-scaling-of-flow-mediated-dilation-is-it-always-helpful
#2
K M McLay, J P Nederveen, J J Koval, D H Paterson, J M Murias
Flow-mediated dilation (FMD) is calculated as the greatest percent change in arterial diameter following an ischaemic challenge. This Traditional %FMD calculation is thought to have statistical bias towards baseline diameter (Dbase ), which is reduced by allometric scaling. This study examined whether allometric scaling FMD influenced the difference between a group of healthy young and older adults compared to the Traditional %FMD, and to determine whether a New (allometric) scaling %FMD improved the ability to obtain individually scaled FMD...
August 13, 2017: Clinical Physiology and Functional Imaging
https://www.readbyqxmd.com/read/28800382/suboptimal-cotrimoxazole-prophylactic-concentrations-in-hiv-infected-children-according-to-the-who-guidelines
#3
C Pressiat, V Mea-Assande, C Yonaba, J-M Treluyer, D-L Dahourou, M Amorissani-Folquet, S Blanche, F Eboua, D Ye, G Lui, K Malateste, Y Zheng, V Leroy, D Hirt
AIMS: A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole (sulfamethoxazole (SMX) and trimethoprim (TMP)) advised by WHO. METHODS: Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/ 40 mg of TMP once daily). Nonlinear mixed effects modelling approach was used to analyze plasma concentrations. Factors that could impact the pharmacokinetic profile were investigate...
August 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28770697/the-ontogenetic-allometry-of-body-morphology-and-chemical-composition-in-dairy-goat-wethers
#4
R A M Vieira, N M Rohem Júnior, R S Gomes, T S Oliveira, L C R Bendia, F H V Azevedo, D L Barbosa, L S Glória, M T Rodrigues
We studied the ontogenetic growth of goat wethers (castrated male goats) of the Saanen and Swiss Alpine breeds based on a large range of intraspecific body mass (BM). The body parts and the chemical constituents of the empty body were described by the allometric function by using BM and the empty body mass (EBM) as the predictors for morphological traits and chemical composition, respectively. We fitted the allometric scaling function by applying the SAS NLMIXED procedure, but to evaluate assumptions regarding variances in morphological and compositional traits, we combined the scaling function with homoscedastic (MOD1), and the heteroscedastic exponential (MOD2) and power-of-the-mean (MOD3) variance functions...
August 3, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28758518/allometric-scaling-of-power-force-velocity-ergometry-profiles-in-men
#5
Hamdi Jaafar
AIM: To examine the appropriate magnitude of allometric scaling of the force-velocity relationship according to body dimensions and to establish normative data for the power-force-velocity relationship for active men. SUBJECTS AND METHODS: Ninety-seven participants completed a force-velocity test on a Monark cycle ergometer. Allometric exponents and percentile ranks were established for maximal power (Pmax), maximal force (F0) and maximal velocity (V0). RESULTS: The mean (± SD) of Pmax, F0 and V0 were 1114...
July 31, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28755396/allometry-and-morphometrics-of-clypeal-membrane-size-and-shape-in-nicrophorus-coleoptera-silphidae
#6
Jillian D Wormington, Barney Luttbeg
Contests between same-sex opponents over resources necessary for reproduction, as well interactions used to discern mate quality, often involve exaggerated traits wherein large individuals have disproportionately larger traits. This positive allometric scaling of weapons or signals facilitates communication during social interactions by accentuating body size differences between individuals. Typically, males carry these exaggerated traits, as males must compete over limited female gametes. However, in Nicrophorus beetles both males and females engage in physical contests over the vertebrate carcasses they need to provision and raise offspring...
July 29, 2017: Journal of Morphology
https://www.readbyqxmd.com/read/28717107/human-plasma-and-urinary-metabolic-profiles-of-trimethylamine-and-trimethylamine-n-oxide-extrapolated-using-a-simple-physiologically-based-pharmacokinetic-model
#7
Makiko Shimizu, Hiroshi Yamazaki
Trimethylamine, a dietary- and medicinal carnitine-derived amine, is extensively metabolized by liver to non-malodorous trimethylamine N-oxide. Although trimethylamine and trimethylamine N-oxide under daily dietary consumption or carnitine treatment are generally regarded as nontoxic, they have been, and remain, of toxicological and clinical interest because of their potential association with atherosclerosis. The aim of the current study was to model the pharmacokinetics of trimethylamine after oral administration of trimethylamine in humans and compare the results with reported measured values...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28690608/phylogenetic-tracings-of-proteome-size-support-the-gradual-accretion-of-protein-structural-domains-and-the-early-origin-of-viruses-from-primordial-cells
#8
Arshan Nasir, Kyung Mo Kim, Gustavo Caetano-Anollés
Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28684371/pharmacokinetics-and-model-based-dosing-to-optimize-fludarabine-therapy-in-pediatric-hematopoietic-cell-transplant-recipients
#9
Vijay Ivaturi, Christopher C Dvorak, Danna Chan, Tao Liu, Morton J Cowan, Justin Wahlstrom, Melisa Stricherz, Cathryn Jennissen, Paul J Orchard, Jakub Tolar, Sung-Yun Pai, Liusheng Huang, Francesca Aweeka, Janel Long-Boyle
A prospective multicenter study was conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of fludarabine plasma (f-ara-a) and intracellular triphosphate (f-ara-ATP) in children undergoing hematopoietic cell transplantation (HCT) and receiving fludarabine with conditioning. Plasma and peripheral blood mononuclear cells (PBMCs) were collected over the course of therapy for quantitation of f-ara-a and f-ara-ATP. Nonlinear mixed-effects modeling was used to develop the PK model, including identification of covariates impacting drug disposition...
July 3, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28681225/a-population-pharmacokinetic-model-to-predict-the-individual-starting-dose-of-tacrolimus-following-pediatric-renal-transplantation
#10
Louise M Andrews, Dennis A Hesselink, Teun van Gelder, Birgit C P Koch, Elisabeth A M Cornelissen, Roger J M Brüggemann, Ron H N van Schaik, Saskia N de Wildt, Karlien Cransberg, Brenda C M de Winter
BACKGROUND: Multiple clinical, demographic, and genetic factors affect the pharmacokinetics of tacrolimus in children, yet in daily practice, a uniform body-weight based starting dose is used. It can take weeks to reach the target tacrolimus pre-dose concentration. OBJECTIVES: The objectives of this study were to determine the pharmacokinetics of tacrolimus immediately after kidney transplantation and to find relevant parameters for dose individualization using a population pharmacokinetic analysis...
July 5, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28681164/influence-of-molecular-size-on-the-clearance-of-antibody-fragments
#11
Zhe Li, Ben-Fillippo Krippendorff, Dhaval K Shah
PURPOSE: To establish a continuous relationship between the size of various antibody fragments and their systemic clearance (CL) in mice. METHODS: Two different orthogonal approaches have been used to establish the relationship. First approach uses CL values estimated by non-compartmental analysis (NCA) to establish a correlation with protein size. The second approach simultaneously characterizes the PK data for all the proteins using a 2-compartment model to establish a relationship between protein size and pharmacokinetic (PK) parameters...
July 5, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28680689/rensching-cats-and-dogs-feeding-ecology-and-fecundity-trends-explain-variation-in-the-allometry-of-sexual-size-dimorphism
#12
P J Johnson, M J Noonan, A C Kitchener, L A Harrington, C Newman, D W Macdonald
The tendency for sexual size dimorphism (SSD) to increase with body mass in taxa where males are larger, and to decrease when females are larger, is known as Rensch's rule. In mammals, where the trend occurs, it is believed to be the result of a competitive advantage for larger males, while female mass is constrained by the energetics of reproduction. Here, we examine the allometry of SSD within the Felidae and Canidae, demonstrating distinctly different patterns: in felids, there is positive allometric scaling, while there is no trend in canids...
June 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28664670/population-pharmacokinetics-of-human-antithrombin-concentrate-in-pediatric-patients
#13
Brady S Moffett, Rosa Diaz, Marianne Galati, Donald Mahoney, Jun Teruya, Donald L Yee
AIMS: Antithrombin is increasingly used in pediatric patients, yet there are few age-specific pharmacokinetic data to guide dosing. We aim to describe the pharmacokinetic profile of human (plasma-derived) antithrombin concentrate in pediatric patients. METHODS: A retrospective review of 5 years of patients < 19 years of age admitted to our institution who received antithrombin concentrate, were not on mechanical circulatory support and had baseline (pre-dose) and post-dose plasma antithrombin activity levels available for analysis, was performed...
June 29, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28653303/the-importance-of-body-mass-normalisation-for-ultrasound-measurements-of-the-morphology-of-oblique-abdominis-muscles-the-effect-of-age-gender-and-sport-practice
#14
Pawel Linek
Some studies have not considered body mass as a confounder in analysis of oblique abdominis muscles (OAM) (including the oblique externus [OE] and oblique internus [OI]), which may have led to improper interpretation of results. To assess the differences in the effect of age, gender, and physical activity between normalised for body mass and actual values of the OAM as well as to establish the effect of age, gender, and physical activity on normalised for body mass OAM thicknesses in adolescents. A real-time ultrasound was used to obtain images of the OAM...
June 27, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28650363/population-pharmacokinetics-and-pharmacodynamic-target-attainment-of-vancomycin-in-neonates-on-extracorporeal-life-support
#15
Jeffrey J Cies, Wayne S Moore, Kristen Nichols, Chad A Knoderer, Dominick M Carella, Arun Chopra
OBJECTIVES: To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary ¼-inch extracorporeal life support circuit with a Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC, Wayne, NJ). DESIGN: Retrospective medical record review. SETTING: Two free-standing tertiary/quaternary pediatric children's hospitals. PATIENTS: Neonates receiving either veno-arterial or veno-venous extracorporeal life support and vancomycin for empiric or definitive therapy with resulting serum concentrations...
June 22, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-and-optimal-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#16
Maxwell T Chirehwa, Helen McIlleron, Roxana Rustomjee, Thuli Mthiyane, Philip Onyebujoh, Peter Smith, Paolo Denti
Pyrazinamide is used in the treatment of tuberculosis (TB) because its sterilizing effect against tubercle bacilli allows the shortening of treatment. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multidrug-resistant tuberculosis (MDR-TB)...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28597978/pharmacokinetics-of-sulfadoxine-and-pyrimethamine-for-intermittent-preventive-treatment-of-malaria-during-pregnancy-and-after-delivery
#17
M de Kock, J Tarning, L Workman, M M Nyunt, I Adam, K I Barnes, P Denti
Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed-effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3-fold for sulfadoxine but decreased by 18% for pyrimethamine...
July 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28555724/population-pharmacokinetics-of-amoxicillin-in-term-neonates-undergoing-moderate-hypothermia
#18
Yuma A Bijleveld, Ron A A Mathôt, Johanna H van der Lee, Floris Groenendaal, Peter H Dijk, Arno van Heijst, Sinno H P Simons, Koen P Dijkman, Henrica L M van Straaten, Monique Rijken, Inge A Zonnenberg, Filip Cools, Alexandra Zecic, Debbie H G M Nuytemans, Anton H van Kaam, Timo R de Haan
The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N=125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3000 g, 2 days PNA (i.e. TEMP 33.5°C), and normal UO, Cl was 0...
May 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28552954/scaling-relationships-of-twig-biomass-allocation-in-pinus-hwangshanensis-along-an-altitudinal-gradient
#19
Man Li, Yuan Zheng, RuiRui Fan, QuanLin Zhong, DongLiang Cheng
Understanding the response of biomass allocation in twigs (the terminal branches of current-year shoots) to environmental change is crucial for elucidating forest ecosystem carbon storage, carbon cycling, and plant life history strategies under a changing climate. On the basis of interspecies investigations of broad-leaved plants, previous studies have demonstrated that plants respond to environmental factors by allocating biomass in an allometric manner between support tissues (i.e., stems) and the leaf biomass of twigs, where the scaling exponent (i...
2017: PloS One
https://www.readbyqxmd.com/read/28547211/sheldon-spectrum-and-the-plankton-paradox-two-sides-of-the-same-coin-a-trait-based-plankton-size-spectrum-model
#20
José A Cuesta, Gustav W Delius, Richard Law
The Sheldon spectrum describes a remarkable regularity in aquatic ecosystems: the biomass density as a function of logarithmic body mass is approximately constant over many orders of magnitude. While size-spectrum models have explained this phenomenon for assemblages of multicellular organisms, this paper introduces a species-resolved size-spectrum model to explain the phenomenon in unicellular plankton. A Sheldon spectrum spanning the cell-size range of unicellular plankton necessarily consists of a large number of coexisting species covering a wide range of characteristic sizes...
May 25, 2017: Journal of Mathematical Biology
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