keyword
MENU ▼
Read by QxMD icon Read
search

pharmacokinetics

keyword
https://www.readbyqxmd.com/read/28109128/population-pharmacokinetics-and-pharmacodynamics-of-benralizumab-in-healthy-volunteers-and-patients-with-asthma
#1
B Wang, L Yan, Z Yao, L K Roskos
Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α, immunoglobulin G (IgG) 1 κ monoclonal antibody. We developed a population pharmacokinetic (PK)/pharmacodynamic (PD) model for benralizumab by analyzing PK and blood eosinophil count data from two healthy volunteer studies (N = 48) and four studies in patients with asthma (N = 152). Benralizumab PK was dose-proportional and adequately described by a two-compartment model with first-order elimination from the central compartment and first-order absorption from the subcutaneous dosing site...
January 21, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28109060/morphine-pharmacodynamics-in-mechanically-ventilated-preterm-neonates-undergoing-endotracheal-suctioning
#2
P A Välitalo, Ehj Krekels, M van Dijk, Shp Simons, D Tibboel, Caj Knibbe
To date, morphine pharmacokinetics (PKs) are well quantified in neonates, but results about its efficacy are ambiguous. This work presents an analysis of a previously published study on pain measurements in mechanically ventilated preterm neonates who received either morphine or placebo to improve comfort during invasive ventilation. The research question was whether morphine reduces the pain associated with endotracheal or nasal suctioning before, during, and after suctioning. Because these neonates cannot verbalize their pain levels, pain was assessed on the basis of several validated pain measurement instruments (i...
January 21, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28108738/spect-and-pet-radiopharmaceuticals-for-molecular-imaging-of-apoptosis-from-bench-to-clinic
#3
Xiaobo Wang, Han Feng, Shichao Zhao, Junling Xu, Xinyu Wu, Jing Cui, Ying Zhang, Yuhua Qin, Zhiguo Liu, Tang Gao, Yongju Gao, Wenbin Zeng
Owing to the central role of apoptosis in many human diseases and the wide-spread application of apoptosis-based therapeutics, molecular imaging of apoptosis in clinical practice is of great interest for clinicians, and holds great promises. Based on the well-defined biochemical changes for apoptosis, a rich assortment of probes and approaches have been developed for molecular imaging of apoptosis with various imaging modalities. Among these imaging techniques, nuclear imaging (including single photon emission computed tomography and positron emission tomography) remains the premier clinical method owing to their high specificity and sensitivity...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108402/using-pharmacokinetic-modelling-to-improve-prescribing-practices-of-intravenous-aminophylline-in-childhood-asthma-exacerbations
#4
Lewis Cooney, Antonia McBride, Andrew Lilley, Ian Sinha, Trevor N Johnson, Daniel B Hawcutt
OBJECTIVE: To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. METHODS: Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. RESULTS: Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those <10 mg/L, and adverse effects occurred in 57%...
January 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28108364/from-natalizumab-to-fingolimod-in-eight-weeks-immunological-clinical-and-radiological-data-in-quest-of-the-optimal-switch
#5
Andrea Harrer, Georg Pilz, Katrin Oppermann, Marlene Sageder, Shahrzad Afazel, Elisabeth Haschke-Becher, Theo Rispens, Annick de Vries, Mark McCoy, Vlado Stevanovic, Wolfgang Hitzl, Eugen Trinka, Jörg Kraus, Johann Sellner, Peter Wipfler
Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28108293/a-model-incorporating-combined-rtis-and-pis-therapy-during-early-hiv-1-infection
#6
Sutimin, F Chirove, E Soewono, N Nuraini, L B Suromo
We develop a within host mathematical model of HIV-1 infection describing the effects of combined RTIs and PIs treatments on early HIV-1 infection when treatment is captured using periodic functions of pharmacokinetics type. We use an alternative of the basic reproduction number to analyze endemicity level of HIV-1 infection. Various treatment scenarios incorporating perfect and imperfect drug adherence in drug administration are explored. Our results show that pharmacokinetics treatment is a more realistic way of administering the treatment...
January 17, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28107923/a-sensitive-and-rapid-uflc-apci-ms-ms-bioanalytical-method-for-quantification-of-endogenous-and-exogenous-vitamin-k1-isomers-in-human-plasma-development-validation-and-first-application-to-a-pharmacokinetic-study
#7
Nagaraj Kumar Nannapaneni, Sunil S Jalalpure, Rajendraprasad Muppavarapu, Sunil Kumar Sirigiri
Due to lack of suitable bioanalytical methods in previous literature, for simultaneous estimation of Vitamin K1 isomers, in compliance with the current regulatory expectation, we aimed to develop a sensitive and rapid method with UFLC-APCI-MS/MS (ultrafast liquid chromatography - tandem mass spectrometry) using human plasma. A simple and cost effective procedure was implemented with the combination of protein precipitation and liquid extraction, to isolate the targets from plasma sample, while achieving an insignificant matrix effects and high recovery (≥88...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107700/comparative-pharmacokinetics-of-eight-major-bioactive-components-in-normal-and-bacterial-diarrhea-mini-pigs-after-oral-administration-of-gegen-qinlian-decoction
#8
Xiao Ling, Yuqiang Xiang, Qingfa Tang, Feilong Chen, Xiaomei Tan
Healthy animals are most widely used in current pharmacokinetic(PK) studies. However, neglecting the effects of specific diseases on drug absorption results in the PK parameters of those experiments not accurately reflecting in vivo drug concentration changes during treatment. In this study, an E. coli infective diarrheal minipig model was applied to explore the pharmacokinetics of Gegen Qinlian decoction (GQD). A simple and rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine the concentrations of the eight GQD components in minipig plasma after intragastric administration of GQD...
January 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28107689/development-and-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-method-for-the-assay-of-tafamidis-in-rat-plasma-application-to-a-pharmacokinetic-study-in-rats
#9
Hun-Chan Hyun, Jong-Woo Jeong, Hye-Rim Kim, Ji-Hoon Oh, Jong-Hwa Lee, Sungwook Choi, Yeon-Soo Kim, Tae-Sung Koo
Tafamidis is a first-in-class inhibitor of transthyretin amyloid fibril formation. It has been available in Argentina, Japan, and Mexico for the treatment of transthyretin amyloidosis in adult patients with early-stage symptomatic polyneuropathy. In this study, a rapid and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the assay of tafamidis in rat plasma. The method was also assessed for its applicability to pharmacokinetic studies in rats. Tafamidis was extracted from rat plasma by the liquid-liquid extraction method using hydrochloric acid and ethyl acetate...
January 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28107561/beta-blockers-for-hypertension
#10
REVIEW
Charles S Wiysonge, Hazel A Bradley, Jimmy Volmink, Bongani M Mayosi, Lionel H Opie
BACKGROUND: Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial...
January 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28106992/discovery-of-n-pyridin-4-yl-1-5-naphthyridin-2-amines-as-potential-tau-pathology-pet-tracers-for-alzheimer-s-disease
#11
Frederik J R Rombouts, José-Ignacio Andrés, Manuela Ariza, José Manuel Alonso, Nigel Austin, Astrid Bottelbergs, Lu Chen, Vladimir Chupakhin, Erna Cleiren, Katleen Fierens, Alberto Fontana, Xavier Langlois, Joseph E Leenaerts, Jonas Mariën, Carolina Martinez Lamenca, Rhys Salter, Mark E Schmidt, Paula Te Riele, Cindy Wintmolders, Andrés A Trabanco, Wei Zhang, Gregor J Macdonald, Diederik Moechars
A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated β-amyloid (Aβ). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with sub-optimal physicochemical properties...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28106991/discovery-of-a-phosphoinositide-3-kinase-pi3k-b-d-inhibitor-for-the-treatment-of-phosphatase-and-tensin-homolog-pten-deficient-tumors-building-pi3kb-potency-in-a-pi3kd-selective-template-by-targeting-non-conserved-asp856
#12
Stéphane Perreault, Jayaraman Chandrasekhar, Zhi-Hua Cui, Jerry B Evarts, Jia Hao, Joshua A Kaplan, Adam Kashishian, Kathleen S Keegan, Thomas Kenney, David J Koditek, Latesh Lad, Eve-Irene Lepist, Mary E McGrath, Leena Patel, Bart Phillips, Joseph Therrien, Jennifer Treiberg, Anella Yahiaoui, Gary Phillips
Phosphoinositide 3-kinase (PI3K) beta signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kbeta/delta inhibitors in which PI3Kbeta potency was built in a PI3Kdelta-selective template. This work led to the discovery of a highly selective PI3Kbeta/delta inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model...
January 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28106796/preparative-scale-resolution-of-enantiomers-enables-accelerated-drug-discovery-and-development
#13
Hanna Leek, Shalini Andersson
The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106709/systemic-pharmacokinetics-and-pharmacodynamics-of-intravitreal-aflibercept-bevacizumab-and-ranibizumab
#14
Robert L Avery, Alessandro A Castellarin, Nathan C Steinle, Dilsher S Dhoot, Dante J Pieramici, Robert See, Stephen Couvillion, Maʼan A Nasir, Melvin D Rabena, Mauricio Maia, Sherri Van Everen, Kha Le, William D Hanley
PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO). METHODS: Prospective, open-label, nonrandomized clinical trial of patients with AMD, DME, or RVO who were antivascular endothelial growth factor (VEGF) naïve or had not received anti-VEGF for ≥4 months. Patients received 3 monthly intravitreal injections of aflibercept 2...
January 18, 2017: Retina
https://www.readbyqxmd.com/read/28106531/preclinical-characterization-of-the-novel-hcv-ns3-protease-inhibitor-gs-9256
#15
Huiling Yang, Chris Yang, Yujin Wang, Gerry Rhodes, Margaret Robinson, Guofeng Cheng, Xiaoping Qi, Hongmei Mo, Yang Tian, Rowchanak Pakdaman, X Christopher Sheng, Choung U Kim, William E Delaney
BACKGROUND: GS-9256 is an inhibitor of hepatitis C virus (HCV) NS3 protease with a macrocyclic structure and novel phosphinic acid pharmacophore. METHODS: Key preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance, and pharmacokinetic properties were investigated in non-human species. RESULTS: In genotype (GT) 1b Huh-luc cells with a replicon encoding luciferase, GS-9256 had a mean EC50 value of 20.0 nM, with minimal cytotoxicity...
January 20, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28105858/hplc-ms-ms-method-for-dexmedetomidine-quantification-with-design-of-experiments-approach-application-to-pediatric-pharmacokinetic-study
#16
Oliwia Szerkus, Wiktoria Struck-Lewicka, Marta Kordalewska, Ewa Bartosińska, Renata Bujak, Agnieszka Borsuk, Agnieszk Bienert, Alicja Bartkowska-Śniatkowska, Justyna Warzybok, Paweł Wiczling, Antoni Nasal, Roman Kaliszan, Mchał Jan Markuszewski, Danuta Siluk
AIM: The purpose of this work was to develop and validate a rapid and robust LC-MS/MS method for the determination of dexmedetomidine (DEX) in plasma, suitable for analysis of a large number of samples. METHOD: Systematic approach, Design of Experiments, was applied to optimize ESI source parameters and to evaluate method robustness, therefore, a rapid, stable and cost-effective assay was developed. The method was validated according to US FDA guidelines. LLOQ was determined at 5 pg/ml...
January 20, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28105598/clinical-pharmacokinetics-and-pharmacodynamics-of-dexmedetomidine
#17
REVIEW
Maud A S Weerink, Michel M R F Struys, Laura N Hannivoort, Clemens R M Barends, Anthony R Absalom, Pieter Colin
Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1 ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug's peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative...
January 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28105513/pharmacokinetics-of-ginkgolides-a-b-and-k-after-single-and-multiple-intravenous-infusions-and-their-interactions-with-midazolam-in-healthy-chinese-male-subjects
#18
Feng Shao, Hongwen Zhang, Lijun Xie, Juan Chen, Sufeng Zhou, Jinsong Zhang, Jinru Lv, Weiwen Hao, Yunsu Ma, Yun Liu, Ning Ou, Wei Xiao
PURPOSE: Ginkgo terpene lactones meglumine injection (GMI) is a novel preparation of traditional Chinese medicine that contains ginkgolides A, B and K (GA, GB, GK, respectively) as its primary components. In this study we evaluated the safety, tolerability and pharmacokinetics of these three ginkgolides after single and multiple intravenous infusions of GMI. We also investigated the effect of GMI on cytochrome P450 3A4 (CYP3A4) in healthy Chinese volunteers. METHODS: In this open-label, placebo-controlled study 15 subjects were randomly assigned to receive GMI or matched placebo (4:1 ratio)...
January 20, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28105500/-discontinuation-of-benzodiazepines-in-old-age-when-and-if-so-how
#19
Dirk K Wolter
Although viewed critically in geriatrics, benzodiazepine use is still common among old people. Before reducing the dosage the following questions must be considered: 1. Are there indications for benzodiazepine treatment and will discontinuation cause relevant rebound symptoms of the initial disorder treated? 2. To what extent do the patient and other key persons consider discontinuation to be reasonable and will they support discontinuation? 3. Is the target complete withdrawal, a dose reduction or shift to another benzodiazepine drug which is more suitable in old age for pharmacokinetic reasons? This article provides assistance in answering these questions and some guidelines for the practical management of discontinuation...
January 19, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28105288/discovery-of-spirocyclic-aldosterone-synthase-inhibitors-as-potential-treatments-for-resistant-hypertension
#20
Whitney L Petrilli, Scott B Hoyt, Clare London, Daniel McMasters, Andreas Verras, Mary Struthers, Doris Cully, Thomas Wisniewski, Ning Ren, Charlene Bopp, Andrea Sok, Qing Chen, Ying Li, Elaine Tung, Wei Tang, Gino Salituro, Ian Knemeyer, Bindhu Karanam, Joseph Clemas, Gaochao Zhou, Jack Gibson, Carrie Ann Shipley, Douglas J MacNeil, Ruth Duffy, James R Tata, Feroze Ujjainwalla, Amjad Ali, Yusheng Xiong
Herein we report the discovery and hit-to-lead optimization of a series of spirocyclic piperidine aldosterone synthase (CYP11B2) inhibitors. Compounds from this series display potent CYP11B2 inhibition, good selectivity versus related CYP enzymes, and lead-like physical and pharmacokinetic properties.
January 12, 2017: ACS Medicinal Chemistry Letters
keyword
keyword
4708
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"