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"Allometric scaling"

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https://www.readbyqxmd.com/read/29470718/prediction-of-human-pharmacokinetics-of-ulixertinib-a-novel-erk1-2-inhibitor-from-mice-rats-and-dogs-pharmacokinetics
#1
Ponnayyan Sulochana Suresh, Ravi Kumar Jairam, Devaraj V Chandrasekhar, Anera Balakrishna Vinod, Rakesh A Hiremath, Anusha Raj, Mohd Zainuddin, Ravi Kanth Bhamidipati, Ramesh Mullangi
BACKGROUND AND OBJECTIVES: Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. The primary objectives of the study were to evaluate the pharmacokinetics of ulixertinib in mice, rats, and dogs followed by prediction of human pharmacokinetic profile by allometric equations with/without correction factors. METHODS: Oral and intravenous pharmacokinetic profiles of ulixertinib were generated in mice, rats, and dogs. The human intravenous pharmacokinetics profiles [volume of distribution (Vss ) and clearance (CL)] were predicted employing simple allometry and using correction factors [maximum life span potential (MLP) and brain weight (BW)]...
February 22, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29469189/incorporation-of-gsta1-genetic-variations-into-a-population-pharmacokinetic-model-for-iv-busulfan-in-paediatric-hematopoietic-stem-cell-transplantation
#2
T Nava, N Kassir, M A Rezgui, C R S Uppugunduri, P Huezo-Diaz Curtis, M Duval, Y Théoret Y, L E Daudt, C Litalien, M Ansari, M Krajinovic, H Bittencourt
AIMS: To develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan imetabolism. METHODS: Busulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.1 to 20) who received intravenous busulfan during the conditioning regimen prior to stem cell transplantation. Weight, sex, baseline disease (malignant vs...
February 22, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29463542/population-pharmacokinetic-properties-of-sulfadoxine-and-pyrimethamine-a-pooled-analysis-to-inform-optimal-dosing-in-african-children-with-uncomplicated-malaria
#3
Miné de Kock, Joel Tarning, Lesley Workman, Elizabeth N Allen, Mamadou M Tekete, Abdoulaye A Djimde, David J Bell, Steve A Ward, Karen I Barnes, Paolo Denti
Sulfadoxine/pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children between 3 to 59 months in the sub-Sahel regions of Africa. Sub-optimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 paediatric and 386 adult patients were analysed using nonlinear mixed effects modelling to evaluate the current dosing regimen and, if needed, propose an optimised dosing regimen in children under five years old...
February 20, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29440734/dynamics-of-starvation-and-recovery-predict-extinction-risk-and-both-damuth-s-law-and-cope-s-rule
#4
Justin D Yeakel, Christopher P Kempes, Sidney Redner
The eco-evolutionary dynamics of species are fundamentally linked to the energetic constraints of their constituent individuals. Of particular importance is the interplay between reproduction and the dynamics of starvation and recovery. To elucidate this interplay, here we introduce a nutritional state-structured model that incorporates two classes of consumers: nutritionally replete, reproducing consumers, and undernourished, nonreproducing consumers. We obtain strong constraints on starvation and recovery rates by deriving allometric scaling relationships and find that population dynamics are typically driven to a steady state...
February 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29438998/hydroxychloroquine-a-physiologically-based-pharmacokinetic-model-in-the-context-of-cancer-related-autophagy-modulation
#5
Keagan P Collins, Kristen M Jackson, Daniel L Gustafson
Hydroxychloroquine (HCQ) is a lysosomotropic autophagy inhibitor being used in over 50 clinical trials either alone or in combination with chemotherapy. Pharmacokinetic (PK) and pharmacodynamic (PD) studies with HCQ have shown that drug exposure in the blood does not correlate with autophagy inhibition in either peripheral blood mononuclear cells (PBMCs) or tumor tissue. To better explain this PK/PD disconnect a physiologically-based pharmacokinetic model (PBPK) was developed for HCQ describing the tissue-specific absorption, distribution, metabolism, and excretion as well as lysosome-specific sequestration...
February 8, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29436715/tnf-%C3%AE-level-affects-etanercept-clearance-tnf-%C3%AE-concentration-as-a-new-correction-factor-of-allometric-scaling-to-predict-individual-etanercept-clearances-in-patients-with-ankylosing-spondylitis
#6
Yuwei Deng, Li Hu, Wei Qiang, Zeneng Cheng, Lei Wang, Xiaoxia Wang
Etanercept (ETN) is a widely used anti- tumor necrosis factor-α (TNF-α) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF-α to inhibit its inflammation effects. In this study, the effect of TNF-α level on ETN clearance (CL) was investigated, and the TNF-α concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF-α concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts...
February 13, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29407773/preclinical-evaluation-of-the-mono-pegylated-recombinant-human-interleukin-11-in-cynomolgus-monkeys
#7
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6...
February 2, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29401304/coordinated-responses-of-plant-hydraulic-architecture-with-the-reduction-of-stomatal-conductance-under-elevated-co2-concentration
#8
Guang-You Hao, N Michele Holbrook, Maciej A Zwieniecki, Vincent P Gutschick, Hormoz BassiriRad
Stomatal conductance (gs) generally decreases under elevated CO2 concentration (eCO2) and its sensitivity varies widely among species, yet the underlying mechanisms for these observed patterns are not totally clear. Understanding these underlying mechanisms, however, is critical for addressing problems regarding plant-environment interactions in a changing climate. We examined gs, water transport efficiency of different components along the whole-plant hydraulic system and allometric scaling in seedlings of six tree species grown under ambient and eCO2 treatments (400 and 600 ppm, respectively)...
February 1, 2018: Tree Physiology
https://www.readbyqxmd.com/read/29378710/evaluation-of-a-system-specific-function-to-describe-the-pharmacokinetics-of-benzylpenicillin-in-term-neonates-undergoing-moderate-hypothermia
#9
Yuma A Bijleveld, Timo R de Haan, Johanna H van der Lee, Floris Groenendaal, Peter H Dijk, Arno van Heijst, Rogier C J de Jonge, 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, Ron A A Mathôt
The pharmacokinetic (PK) properties of i.v. benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as to date these are unknown. To do so, a system-specific modeling approach was applied, in which our recently developed covariate model describing developmental and temperature induced changes in amoxicillin clearance (CL) in the same patient study population, was incorporated into a population PK model of benzylpenicillin with a priori birthweight (BW) based allometric scaling...
January 29, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29363223/the-allometric-scaling-of-body-mass-and-height-in-children-and-adolescents-in-five-countries
#10
Camila Medeiros da Silva Mazzeti, Jéssica Cumpian Silva, Ana Elisa Madalena Rinaldi, Wolney Lisbôa Conde
OBJECTIVE: The purpose a methodology that excludes values outside of the expected spectrum for age (VOESA) of height and body mass in the definition of power (p) to construct an international allometric body mass index (AI) for children and adolescents. METHODS: Datasets of national surveys including individuals (aged 0-19 years) from five countries (Brazil, South Korea, Mexico, England, and the USA) were selected. The p was defined for each country, age range, and sex after exclusion of VOESA for height and weight by log-log linear regression, where β represented p...
January 23, 2018: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/29363050/effect-of-age-related-factors-on-the-pharmacokinetics-of-lamotrigine-and-potential-implications-for-dose-optimisation-in-epilepsy-patients
#11
Sven C van Dijkman, Nico C B de Jager, Willem M Rauwé, Meindert Danhof, Oscar Della Pasqua
BACKGROUND AND AIMS: In this study, we evaluate the performance of allometric concepts to predict the implications of age and size on the pharmacokinetics of lamotrigine, and assess the dose rationale across different age groups from 0.2 to 91 years. METHODS: An allometrically scaled pharmacokinetic model was developed using adolescent and adult data, taking into account the effect of comedications. Model parameters were then used to extrapolate lamotrigine pharmacokinetics to older adults (> 65 years), children (4-12 years) and infants and toddlers (0...
January 23, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29351015/temperature-dependent-growth-and-fission-rate-plasticity-drive-seasonal-and-geographic-changes-in-body-size-in-a-clonal-sea-anemone
#12
Will H Ryan
The temperature-size rule is a commonly observed pattern where adult body size is negatively correlated with developmental temperature. In part, this may occur as a consequence of allometric scaling, where changes in the ratio of surface area to mass limit oxygen diffusion as body size increases. As oxygen demand increases with temperature, a smaller body should be favored as temperature increases. For clonal animals, small changes in growth and/or fission rate can rapidly alter the average body size of clonal descendants...
February 2018: American Naturalist
https://www.readbyqxmd.com/read/29347385/organization-and-scaling-in-water-supply-networks
#13
Likwan Cheng, Bryan W Karney
Public water supply is one of the society's most vital resources and most costly infrastructures. Traditional concepts of these networks capture their engineering identity as isolated, deterministic hydraulic units, but overlook their physics identity as related entities in a probabilistic, geographic ensemble, characterized by size organization and property scaling. Although discoveries of allometric scaling in natural supply networks (organisms and rivers) raised the prospect for similar findings in anthropogenic supplies, so far such a finding has not been reported in public water or related civic resource supplies...
December 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346442/comparative-metabolic-ecology-of-tropical-herbivorous-echinoids-on-a-coral-reef
#14
Levi S Lewis, Jennifer E Smith, Yoan Eynaud
BACKGROUND: The metabolic rate of consumers is a key driver of ecosystem dynamics. On coral reefs, herbivorous echinoids consume fleshy algae, facilitating the growth of reef-building calcified organisms; however, little is known about differences among species in their metabolic and functional ecology. Here, we used log-linear (log-log) regression models to examine the allometric scaling of mass and routine metabolic rate for five common herbivorous echinoids on a Hawaiian coral reef: Echinothrix calamaris, E...
2018: PloS One
https://www.readbyqxmd.com/read/29337897/long-term-mechanical-behavior-of-nano-silica-sol-grouting
#15
Dongjiang Pan, Nong Zhang, Chenghao Zhang, Deyu Qian, Changliang Han, Sen Yang
The longevity of grouting has a significant effect on the safe and sustainable operation of many engineering projects. A 500-day experiment was carried out to study the long-term mechanical behavior of nano silica sol grouting. The nano silica sol was activated with different proportions of a NaCl catalyst and cured under fluctuating temperature and humidity conditions. The mechanical parameters of the grout samples were tested using an electrohydraulic uniaxial compression tester and an improved Vicat instrument...
January 16, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29335617/cardiovascular-function-of-modern-pigs-does-not-comply-with-allometric-scaling-laws
#16
Gerard J van Essen, Maaike Te Lintel Hekkert, Oana Sorop, Ilkka Heinonen, Jolanda van der Velden, Daphne Merkus, Dirk J Duncker
Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has been proposed as a critical factor contributing to the reduced adaptability of modern pigs to stress. Here we tested the hypothesis that cardiac dimensions and pump function in modern heavy farm pigs are disproportionally low for their body weight, and investigated potential underlying mechanisms. The results from the present study indeed demonstrate disproportionally low values for stroke volume and cardiac output in pigs with bodyweights over 150 kg...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311071/population-pharmacokinetics-of-polymyxin-b-in-acutely-ill-adult-patients
#17
Cristina Miglis, Nathaniel J Rhodes, Sean Avedissian, Christine J Kubin, Michael T Yin, Brian Nelson, Manjunath P Pai, Marc H Scheetz
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect and contemporary pharmacokinetic (PK) data is limited. This study sought to evaluate PB exposure differences in various load and non-loading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using LC-MS/MS. Compartmental PK models with linear and allometric scaling of TBW were explored...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29243890/the-evolution-of-floral-ontogenetic-allometry-in-the-andean-genus-caiophora-loasaceae-subfam-loasoideae
#18
Marina Micaela Strelin, Santiago Benitez-Vieyra, Juan Fornoni, Christian Peter Klingenberg, Andrea Cocucci
The astounding variety of angiosperm flower morphologies has evolved in response to many selective forces. Flower development is highly coordinated and involves developmental associations between size and shape, ontogenetic allometry, which in turn affect the morphology of mature flowers. Although ontogenetic allometries can act as a developmental constraint and may influence adaptive evolution, allometries can evolve themselves and may change rapidly in response to selection. We explored the evolution of ontogenetic allometry in the flowers of 11 species of Loasoideae...
December 15, 2017: Evolution & Development
https://www.readbyqxmd.com/read/29227461/population-pharmacokinetics-of-lopinavir-in-severely-malnourished-hiv-infected-children-and-the-effect-on-treatment-outcomes
#19
Moherndran Archary, Helen Mcllleron, Raziya Bobat, Phillip La Russa, Thobekile Sibaya, Lubbe Wiesner, Stefanie Hennig
BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiological changes due to malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomised to early or delayed initiation of lopinavir/ritonavir, abacavir and lamivudine using WHO weight-band dosage charts...
December 8, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29223494/dental-functional-morphology-predicts-the-scaling-of-chewing-rate-in-mammals
#20
Indrė Žliobaitė, Mikael Fortelius
How food intake and mastication scale to satisfy the metabolic needs of mammals has been the subject of considerable scientific debate. Existing theory suggests that the negative allometric scaling of metabolic rate with body mass is compensated by a matching allometric scaling of the chewing rate. Why empirical studies have found that the scaling coefficients of the chewing rate seem to be systematically smaller than expected from theory remains unknown. Here we explain this imparity by decoupling the functional surface area of teeth from overall surface area...
November 27, 2017: Journal of Biomechanics
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