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https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-optimising-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#1
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 sterilising effect against tubercle bacilli allows treatment shortening. 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 multi-drug resistant tuberculosis(MDR-TB)...
June 12, 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
#2
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...
June 9, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28555724/population-pharmacokinetics-of-amoxicillin-in-term-neonates-undergoing-moderate-hypothermia
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28546466/changes-in-brachial-artery-endothelial-function-and-resting-diameter-with-moderate-intensity-continuous-but-not-sprint-interval-training-in-sedentary-men
#6
Ninette Shenouda, Jenna B Gillen, Martin J Gibala, Maureen J MacDonald
Moderate-intensity continuous training (MICT) improves peripheral artery function in healthy adults, a phenomenon that reverses as continued training induces structural remodeling. Sprint interval training (SIT) elicits physiological adaptations similar to MICT despite a lower exercise volume and time-commitment; however, its effect on peripheral artery function and structure is largely unexplored. We compared peripheral artery responses to 12 weeks of MICT and SIT in sedentary, healthy men (age=27±8 years)...
May 25, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28526601/model-based-precision-dosing-of-sirolimus-in-pediatric-patients-with-vascular-anomalies
#7
Tomoyuki Mizuno, Chie Emoto, Tsuyoshi Fukuda, Adrienne M Hammill, Denise M Adams, Alexander A Vinks
Sirolimus is the first drug to show efficacy in the treatment of patients with complicated vascular anomalies. The current study expands on the evolution of a PK model-based strategy for the precision dosing of sirolimus as part of prospective concentration controlled clinical trials in pediatric patients with vascular anomalies. Twelve month follow up data collected from 52 pediatric patients participating in the Phase 2 clinical trial were analyzed. Target attainment across the age range of 3weeks to 18years after 2-3months of therapy was 94% (49 out of 52 patients)...
May 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28510304/flip-flop-phenomenon-in-epidural-sufentanil-pharmacokinetics-a-population-study-in-children-and-infants
#8
Agnieszka Borsuk, Bogumiła Wołoszczuk-Gębicka, Alicja Bartkowska-Śniatkowska, Jowita Rosada-Kurasińska, Agnieszka Bienert, Paweł Wiczling
The aims of this study were to develop a population pharmacokinetic model of sufentanil coadministered with 0.2% ropivacaine as an epidural infusion in infants and describe the sufentanil absorption profile from epidural space. Data from 2 previously published studies were merged for analysis-20 infants aged 3-36 months receiving sufentanil as an epidural infusion and 41 children 0-17 years old receiving sufentanil as a long-term intravenous infusion. A population nonlinear mixed-effects model was built in NONMEM...
May 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28509794/an-allometric-model-of-remifentanil-pharmacokinetics-and-pharmacodynamics
#9
Douglas J Eleveld, Johannes H Proost, Hugo Vereecke, Anthony R Absalom, Erik Olofsen, Jaap Vuyk, Michel M R F Struys
BACKGROUND: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide range of age and weight. METHODS: Remifentanil pharmacokinetic data were obtained from three previously published studies of adults and children, one of which also contained pharmacodynamic data from adults...
June 2017: Anesthesiology
https://www.readbyqxmd.com/read/28503815/body-mass-normalization-for-lateral-abdominal-muscle-thickness-measurements-in-adolescent-athletes
#10
Pawel Linek
OBJECTIVES: To determine the value of allometric parameters for ultrasound measurements of the oblique external (OE), oblique internal (OI), and transversus abdominis (TrA) muscles in adolescent athletes. The allometric parameter is the slope of the linear regression line between the log-transformed body mass and log-transformed muscle size measurement. METHODS: The study included 114 male adolescent football players between the ages of 10 and 19 years. All individuals with no surgical procedures performed on the trunk area and who had played a sport for at least 2 years were included...
May 15, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28489686/scaling-the-oxygen-uptake-efficiency-slope-for-body-size-in-cystic-fibrosis
#11
Owen William Tomlinson, Alan Robert Barker, Patrick John Oades, Craig Anthony Williams
PURPOSE: The aim of this study was to describe the relationship between body size and the oxygen uptake efficiency slope (OUES) in paediatric patients with cystic fibrosis (CF) and healthy controls (CON), in order to identify appropriate scaling procedures to adjust the influence of body size upon OUES. METHODS: The OUES was derived using maximal and submaximal points from cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was subsequently scaled for stature, body mass (BM) and body surface area (BSA) using ratio-standard (Y/X) and allometric (Y/X) methods...
May 9, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28487524/vertebral-bone-microarchitecture-and-osteocyte-characteristics-of-three-toothed-whale-species-with-varying-diving-behaviour
#12
Tim Rolvien, Michael Hahn, Ursula Siebert, Klaus Püschel, Hans-Joachim Wilke, Björn Busse, Michael Amling, Ralf Oheim
Although vertebral bone microarchitecture has been studied in various tetrapods, limited quantitative data are available on the structural and compositional changes of vertebrae in marine mammals. Whales exhibit exceptional swimming and diving behaviour, and they may not be immune to diving-associated bone pathologies. Lumbar vertebral bodies were analysed in three toothed whale species: the sperm whale (Physeter macrocephalus), orca (Orcinus orca) and harbour porpoise (Phocoena phocoena). The bone volume fraction (BV/TV) did not scale with body size, although the trabeculae were thicker, fewer in number and further apart in larger whale species than in the other two species...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28452143/zy15557-a-novel-long-acting-inhibitor-of-dipeptidyl-peptidase-4-for-the-treatment-of-type-2-diabetes-mellitus
#13
Mukul R Jain, Amit A Joharapurkar, Samadhan G Kshirsagar, Vishal J Patel, Rajesh H Bahekar, Harilal V Patel, Pradip A Jadav, Pankaj R Patel, Ranjit C Desai
BACKGROUND AND PURPOSE: Dipeptidyl peptidase (DPP)-4 inhibitors increase levels of glucagon-like peptide-1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. As longer acting inhibitors have therapeutic advantages, we developed a novel DPP-4 inhibitor, ZY15557, that has a sustained action and long half-life. EXPERIMENTAL APPROACH: We studied the potency, selectivity, efficacy and duration of action of ZY15557, in vitro, with assays of DPP-4 activity...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28442326/inhaled-efficacious-dose-translation-from-rodent-to-human-a-retrospective-analysis-of-clinical-standards-for-respiratory-diseases
#14
REVIEW
J E Phillips
Clinical pharmacologists and toxicologists are often faced with predicting equivalent dosages for humans from biological observations in laboratory animals. Allometric scaling has been used extensively as the basis for extrapolation of drug dosage that might be expected to produce the equivalent biological effects. Allometry is the study of size and its consequences and it is based on the anatomical, physiological, and biochemical similarities between animals. In this review, retrospective analyses have been performed based on data reported in the literature in an attempt to determine the utility of allometric scaling for human dose projections from pre-clinical data for compounds that are delivered by inhalation...
April 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28438921/null-expectations-for-disease-dynamics-in-shrinking-habitat-dilution-or-amplification
#15
Christina L Faust, Andrew P Dobson, Nicole Gottdenker, Laura S P Bloomfield, Hamish I McCallum, Thomas R Gillespie, Maria Diuk-Wasser, Raina K Plowright
As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win-win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model...
June 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28421387/pharmacokinetics-of-monoclonal-antibodies-and-fc-fusion-proteins
#16
REVIEW
Liming Liu
There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life...
April 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28419277/prevention-of-tb-using-rifampicin-plus-isoniazid-reduces-nevirapine-concentrations-in-hiv-exposed-infants
#17
Helen McIlleron, Paolo Denti, Silvia Cohn, Fildah Mashabela, Jennifer D Hoffmann, Saba Shembe, Regina Msandiwa, Lubbe Wiesner, Sithembiso Velaphi, Sanjay G Lala, Richard E Chaisson, Neil Martinson, Kelly E Dooley
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis...
April 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28417561/population-pharmacokinetics-of-morphine-in-patients-with-nonalcoholic-steatohepatitis-nash-and-healthy-adults
#18
V Pierre, C K Johnston, B C Ferslew, Klr Brouwer, D Gonzalez
Altered expression and function of transporters in nonalcoholic steatohepatitis (NASH) patients may affect the pharmacokinetics (PK), efficacy, and safety of substrate drugs. A population pharmacokinetic (PopPK) analysis was performed to assess differences in morphine and morphine-3-glucuronide (M3G) disposition in NASH and healthy subjects. A total of 315 serum and 42 urine samples from 21 subjects (14 healthy; 7 NASH) were analyzed using NONMEM. Morphine and M3G PK were described by three- and one-compartment models, respectively...
May 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28412400/prediction-of-losartan-active-carboxylic-acid-metabolite-exposure-following-losartan-administration-using-static-and-physiologically-based-pharmacokinetic-models
#19
Hoa Q Nguyen, Jian Lin, Emi Kimoto, Ernesto Callegari, Susanna Tse, R Scott Obach
The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under the time-concentration curve ratio (AUCm/AUCp) and their PK profiles in humans using in vitro data when active transport processes are involved in disposition. The strategy was applied to losartan and its pharmacologically active metabolite carboxylosartan as test compounds. Hepatobiliary transport including transport-mediated uptake, canilicular and basolateral efflux, and metabolic clearance estimates were obtained from in vitro studies using human liver microsomes and sandwich cultured hepatocytes...
April 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28408153/refinement-of-the-oral-exposure-description-in-the-cyclic-siloxane-pbpk-model-for-rats-and-humans-implications-for-exposure-assessment
#20
Jerry L Campbell, Melvin E Andersen, Cynthia Van Landingham, Robinan Gentry, Elke Jensen, Jean Y Domoradzki, Harvey J Clewell
The multi-compound, and multi-dose (MC-MD) route physiologically based pharmacokinetic (PBPK) model for cyclic siloxanes reported by McMullin et al. (2016) brought together the series of models for octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in rat and human into a unified code structure that would allow simulation of both compounds following the inhalation and dermal routes of exposure. The refined MC-MD PBPK model presented here expands upon this effort to include representation of rat kinetic data in plasma, tissues and exhaled breath for the parent compounds after oral bolus administration...
April 10, 2017: Toxicology Letters
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