Ying Liu, Maksym Popov, Igor Zavislyak, Hongwei Qu, T Zhang, Jitao Zhang, M R Page, A M Balbashov, G Srinivasan
This report is on the observation and theory of electric field E induced non-linear magnetoelectric (NLME) effects in single crystal platelets of ferrimagnetic M-type strontium aluminum hexagonal ferrite. Using microwave measurement techniques, it was found that a DC electric field along the hexagonal c-axis results in significant changes in the saturation magnetization and uniaxial magneto-crystalline anisotropy field and these changes are proportional to the square of the applied static electric field. The NLME effects were present with or without an external bias magnetic field...
April 22, 2021: Scientific Reports
Raphaël Crépin, Claire Morin, Aurélie Montmartin, Brigitte Tardy-Poncet, Pierre Chelle
The thrombin generation (TG) assay is a well-established tool to capture the clotting potential of any healthy or haemophiliac subject. It measures ex vivo the kinetics of thrombin activation throughout the coagulation. Clinical studies allowed to create two databases gathering the coagulation factor levels and the thrombin generation profile of 40 healthy and 40 haemophiliac A (HA) subjects. Besides, portions of all HA samples were spiked with increasing levels of a TFPI antibody (considered as a possible therapeutic target) and corresponding TG profiles were determined...
April 12, 2021: Journal of Pharmacokinetics and Pharmacodynamics
Guohai Zhou, Lang Wu
Nonlinear mixed-effects (NLME) models are commonly used in longitudinal studies such as pharmacokinetics and HIV viral dynamics studies. NLME models are often derived based on underlying data-generating mechanisms, therefore the parameters in these models often have natural physical interpretations that may suggest reasonable constraints on certain parameters. For example, the HIV viral decay rates for populations receiving anti-HIV treatments may be reasonably expected to be nonnegative. Hypothesis testing for these parameters should incorporate practically reasonable constraints to increase statistical power...
April 5, 2021: Statistics in Medicine
Jennifer H Yu, Mark G Papich, Rodrigo Garcés Torres, Jessica Emerson, Matthew E Kinney, Kelly Helmick, Adrienne Crosier, Carlos R Sanchez, Suzan Murray
Cefovecin is a third-generation cephalosporin with potential value for use in exotic felids due to its long duration of action. A sparse sampling protocol was implemented with 18 zoo-housed cheetahs (Acinonyx jubatus) to evaluate the pharmacokinetics of cefovecin (Convenia® ) after a single 8 mg/kg intramuscular injection. Blood was collected serially for 15 days following administration, and plasma cefovecin concentrations were determined using high-pressure liquid chromatography with ultraviolet detection...
March 28, 2021: Journal of Veterinary Pharmacology and Therapeutics
Jingjing Huang, Xiaoli Wang, Chenxia Hao, Wanhua Yang, Weixia Zhang, Jialin Liu, Hongping Qu
Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14 days were retrospectively enrolled...
March 16, 2021: Internal and Emergency Medicine
Marjolaine Giroux, Nicolas Bouchard, Anik Henderson, Lesly Lam, Van Anh Sylvie Tran, Denis Projean, Jean-François Tessier, Laurence Lepage, Paul Gavra, Georges Ouellet, Michel Vallée, Jean-Philippe Lafrance
Background and Objectives: There is a renewed interest in the successful use of aminoglycosides due to increasing resistance in gram-negative infections. Few studies to date have examined the pharmacokinetics (PK) of intradialytic infusions of tobramycin. This study sought to characterize the pharmacokinetic profile of intradialytically administered tobramycin in infected patients receiving chronic intermittent hemodialysis and to determine whether it is possible to achieve favorable PK targets...
2021: Canadian Journal of Kidney Health and Disease
Silke Gastine, Juanita Pang, Florencia A T Boshier, Simon J Carter, Dagan O Lonsdale, Mario Cortina-Borja, Ivan F N Hung, Judy Breuer, Frank Kloprogge, Joseph F Standing
SARS-CoV-2 viral loads change rapidly following symptom onset so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient-level meta-analysis of SARS-CoV-2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to-date. This systematic review identified case reports, case series and clinical trial data from publications between 1/1/2020 and 31/5/2020 following PRISMA guidelines. A multivariable Cox proportional hazards regression model (Cox-PH) of time to viral clearance was fitted to respiratory and stool samples...
February 28, 2021: Clinical Pharmacology and Therapeutics
Taylor M Gregory, Craig A Harms, Melinda A Gorges, Gregory A Lewbart, Mark G Papich
Ketorolac is a non-steroidal anti-inflammatory drug administered as an analgesic in humans. It has analgesic effects comparable to opioids but without adverse effects such as respiratory depression or restrictions because of controlled drug status. We designed this study to examine the potential of ketorolac as an analgesic for sea turtle rehabilitative medicine. Our objective was to determine the pharmacokinetics of a single 0.25 mg/kg intramuscular dose of ketorolac in a population of 16 captive-raised juvenile loggerhead sea turtles (Caretta caretta)...
February 18, 2021: Journal of Veterinary Pharmacology and Therapeutics
Mei Yang, Libo Zhao, Xiaohui Wang, Chen Sun, Hengmiao Gao, Xiaoling Wang, Suyun Qian
Linezolid is an oxazolidinone antibiotic exhibiting efficacy against multidrug-resistant (MDR) Gram-positive-related infections. However, its population pharmacokinetic (PopPK) profile in Chinese critically ill children has not been characterized. Optimal dosing regimens should be established according to the PopPK/pharmacodynamic(PD) properties of linezolid in the specific population. This work aims to describe the pharmacokinetic (PK) properties of linezolid, assess the factors affecting interpatient variability, and establish an optimized regimen for children in pediatric intensive care unit (PICU)...
February 8, 2021: Antimicrobial Agents and Chemotherapy
Gowooni Park, Hyungsub Kim, Kyun-Seop Bae
SAS® is commonly used for bioequivalence (BE) data analysis. R is a free and open software for general purpose data analysis, and is less frequently used than SAS® for BE data analysis. This tutorial explains how R can be used for BE data analysis to generate comparable results with SAS® . The main SAS® procedures for BE data analysis are PROC GLM and PROC MIXED, and the corresponding R main packages are "sasLM" and "nlme" respectively. For fixed effects only or balanced data, the SAS® PROC GLM and R "sasLM" provide good estimates; however, for a mixed-effects model with unbalanced data, the SAS® PROC MIXED and R "nlme" are better for providing estimates without bias...
December 2020: Translational and clinical pharmacology
Xinyan Zhang, Nengjun Yi
BACKGROUND: Microbiome/metagenomic data have specific characteristics, including varying total sequence reads, over-dispersion, and zero-inflation, which require tailored analytic tools. Many microbiome/metagenomic studies follow a longitudinal design to collect samples, which further complicates the analysis methods needed. A flexible and efficient R package is needed for analyzing processed multilevel or longitudinal microbiome/metagenomic data. RESULTS: NBZIMM is a freely available R package that provides functions for setting up and fitting negative binomial mixed models, zero-inflated negative binomial mixed models, and zero-inflated Gaussian mixed models...
October 30, 2020: BMC Bioinformatics
Jianzhong Wang, Benjamin K Schneider, Hongzhi Xiao, Jicheng Qiu, Xiaohui Gong, Yeon-Jung Seo, Jing Li, Jonathan P Mochel, Xingyuan Cao
The objective of this study was to develop a non-linear mixed-effects (NLME) model to describe the disposition kinetics of vitacoxib in cats following intravenous (I.V) and oral (P.O) (single and multiple) dosing. Data from six consecutive studies with 16 healthy neutered domestic short hair cats were pooled together to build a pharmacokinetic (PK) model using NLME. Population PK parameters were estimated using the stochastic approximation expectation maximization (SAEM) algorithm implemented in Monolix 2019R2...
2020: Frontiers in Veterinary Science
Heather C Kittrell, Jonathan P Mochel, Justin T Brown, Anna Marie K Forseth, Kristen P Hayman, Suzanne M Rajewski, Johann F Coetzee, Benjamin K Schneider, Brette Ratliffe, Kristin J Skoland, Locke A Karriker
Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2...
2020: Frontiers in Veterinary Science
A P Woodward, D Morin, T Whittem
Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis...
September 10, 2020: Journal of Dairy Science
Xiaoling Cheng, Yiming Zhao, Hao Gu, Libo Zhao, Yannan Zang, Xiaoling Wang, Runhui Wu
The narrow therapeutic index and large inter-individual variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring (TDM) necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with immune cytopenia. The objective of this study was to characterize the PK of sirolimus in pediatric patients with immune cytopenia and to develop a population PK model in Chinese children and evaluate its utility for dose individualization...
January 2020: International Journal of Immunopathology and Pharmacology
Jun Zhang, Dandan Wang, Liwei Zou, Min Xiao, Yufeng Zhang, Ziwei Li, Ling Yang, Guangbo Ge, Zhong Zuo
In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since ( S )-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats...
June 2020: Journal of Pharmaceutical Analysis
Peile Wang, Qiwen Zhang, Zhenfeng Zhu, Min Feng, Tongwen Sun, Jing Yang, Xiaojian Zhang
Polymyxin B is used as a last therapeutic option for the treatment of multidrug-resistant Gram-negative bacterial infections. This study aimed to develop a population pharmacokinetic model and limited sampling strategy, a method to estimate the area under the concentration curve (AUC) by using a limited number of samples, to assist therapeutic drug monitoring of polymyxin B in Chinese patients. Population pharmacokinetic analysis was performed using Phoenix® NLME with data obtained from 46 adult patients at steady state...
2020: Frontiers in Pharmacology
Hao Xu, Zhanjun Wang, Ying Li, Jianlong He, Xudong Wu
The Caragana korshinskii shrub is a widely distributed plant found in arid regions and plays an important role in ecological environment protection. Accurate estimations of shrub biomass are particularly important for natural resource management decision making. 114 individual C. korshinskii shrubs from three regions were collected in northwest China in this study. With regions as fixed (dummy variables) and random effects, the nonlinear least square (NLS) regression approach, nonlinear fixed effects (NLFE) approach and nonlinear mixed effects (NLME) approach were developed to predict dynamic growth of total, aboveground, stem, foliage, and root biomass values of C...
September 1, 2020: Journal of Environmental Management
Junichi Nakagawa, Keinosuke Ishido, Yuka Tono, Norihisa Kimura, Taiichi Wakiya, Yuji Okamura, Kenichi Hakamada, Takenori Niioka
BACKGROUND AND OBJECTIVE: Tacrolimus clearance (CL) is significantly altered according to recovery of liver function at an early stage after living donor liver transplantation (LDLT). In this study, we aimed to examine the impact of the change rate from postoperative day (POD) 1 in CL (ΔCL) of tacrolimus during continuous intravenous infusion (CIVI) on recipient recovery. METHODS: A tacrolimus population pharmacokinetic model on POD1 after LDLT was developed using Phoenix NLME 1...
June 8, 2020: European Journal of Drug Metabolism and Pharmacokinetics
Jiashan Zhang, Ying Zan, Hua Huo, Yanfang Liu, Yunbiao Tang, Yaling Han
Nifekalant is a class III antiarrhythmic drug, and its major adverse effect is prolongation of the QT interval. This study analysed data generated from a pharmacokinetic (PK) study to develop a population PK/pharmacodynamics (PD) model for describing the relationship between plasma concentrations and prolongation of the QT interval over time following intravenous administration of nifekalant. This open-labelled, phase I clinical study comprised two dose level groups of eight healthy Chinese volunteers. Concentrations of nifekalant in plasma samples collected at set time-points were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method...
May 23, 2020: European Journal of Pharmaceutical Sciences
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