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https://www.readbyqxmd.com/read/29332251/clinical-pharmacokinetics-and-pharmacodynamics-of-telavancin-compared-with-the-other-glycopeptides
#1
REVIEW
Valentin Al Jalali, Markus Zeitlinger
Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented...
January 13, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29330783/clinical-pharmacokinetics-and-pharmacodynamics-of-infliximab-in-the-treatment-of-inflammatory-bowel-disease
#2
REVIEW
Amy Hemperly, Niels Vande Casteele
Infliximab was the first monoclonal antibody to be approved for the treatment of pediatric and adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC). It has been shown to induce and maintain both clinical remission and mucosal healing in pediatric and adult patients with inflammatory bowel disease (IBD) who are unresponsive or refractory to conventional therapies. The administration of infliximab is weight-based and the drug is administered intravenously. The volume of distribution of infliximab is low and at steady state ranges from 4...
January 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#3
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329709/characterization-of-singly-and-multiply-pegylated-insulin-isomers-by-reversed-phase-ultra-performance-liquid-chromatography-interfaced-with-ion-mobility-mass-spectrometry
#4
Selim Gerislioglu, Scott R Adams, Chrys Wesdemiotis
Conjugation of poly(ethylene glycol) (PEG) to protein drugs (PEGylation) is increasingly utilized in the biotherapeutics field because it improves significantly the drugs' circulatory half-life, solubility, and shelf-life. The activity of a PEGylated drug depends on the number, size, and location of the attached PEG chain(s). This study introduces a 2D separation approach, including reversed-phase ultra-performance liquid chromatography (RP-UPLC) and ion mobility mass spectrometry (IM-MS), in order to determine the structural properties of the conjugates, as demonstrated for a PEGylated insulin sample that was prepared by random amine PEGylation...
April 3, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29329501/sustained-plasma-hepcidin-suppression-and-iron-elevation-by-anticalin-derived-hepcidin-antagonist-in-cynomolgus-monkey
#5
Andreas M Hohlbaum, Hendrik Gille, Stefan Trentmann, Maria Kolodziejczyk, Barbara Rattenstetter, Coby M Laarakkers, Galina Katzmann, Hans Jürgen Christian, Nicole Andersen, Andrea Allersdorfer, Shane A Olwill, Bernd Meibohm, Laurent P Audoly, Dorine W Swinkels, Rachel P L van Swelm
BACKGROUND AND PURPOSE: Anaemia of chronic disease (ACD) has been linked to iron restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here we report the engineering of the human lipocalin-derived, small protein-based Anticalin PRS-080 hepcidin antagonist with high affinity and selectivity. EXPERIMENTAL APPROACH: Anticalin- and hepcidin-specific pharmacokinetic/pharmacodynamic modelling was used to design and select the suitable drug candidate based on half life extension and duration of hepcidin suppression...
January 12, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29329072/development-of-potent-and-proteolytically-stable-human-neuromedin-u-receptor-agonists
#6
An De Prins, Charlotte Martin, Yannick Van Wanseele, Louise Julie Skov, Csaba Tömböly, Dirk Tourwé, Vicky Caveliers, Ann Van Eeckhaut, Birgitte Holst, Mette Marie Rosenkilde, Ilse Smolders, Steven Ballet
Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a wide range of physiological processes such as regulation of feeding behavior, the stress response and nociception. The major limitation to use NMU as a therapeutic is its short half-life. Here, we describe the development of a set of novel NMU-analogs based on NMU-8, by introducing unnatural amino acids into the native sequence. This approach shows that it is possible to generate molecules with increased potency and improved plasma stability without major changes of the peptidic nature or the introduction of large conjugates...
December 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29329004/contemporary-enzyme-based-technologies-for-bioremediation-a-review
#7
REVIEW
Babita Sharma, Arun Kumar Dangi, Pratyoosh Shukla
The persistent disposal of xenobiotic compounds like insecticides, pesticides, fertilizers, plastics and other hydrocarbon containing substances is the major source of environmental pollution which needs to be eliminated. Many contemporary remediation methods such as physical, chemical and biological are currently being used, but they are not sufficient to clean the environment. The enzyme based bioremediation is an easy, quick, eco-friendly and socially acceptable approach used for the bioremediation of these recalcitrant xenobiotic compounds from the natural environment...
January 9, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29328653/extending-half-life-of-h-ferritin-nanoparticle-by-fusing-albumin-binding-domain-for-doxorubicin-encapsulation
#8
Chunyue Wang, Chun Zhang, Zenglan Li, Shuang Yin, Qi Wang, Fangxia Guo, Yao Zhang, Rong Yu, Yongdong Liu, Zhiguo Su
Nanoparticles based on the heavy chain of the human ferritin (HFn) are arousing growing interest in the field of drug-delivery due to their exceptional characteristics. However, the unsatisfied plasma half-life of HFn substantially limits its application as a delivery platform for anti-tumor agents. Herein, we fused an albumin binding domain (ABD) variant which basically derives from the streptococcal protein G and possesses a long-acting characteristic in serum albumin to the N-terminus of the HFn for the aim of half-life extension...
January 12, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29327960/pharmacokinetics-of-a-single-intramuscular-injection-of-long-acting-ceftiofur-crystalline-free-acid-in-cattle-egrets-bubulcus-ibis
#9
Jennifer A Waldoch, Sherry K Cox, Douglas L Armstrong
We determined the pharmacokinetic properties of ceftiofur crystalline-free acid (CCFA), a long-acting antibiotic, after a single intramuscular injection in cattle egrets ( Bubulcus ibis). A dose of 20 mg/kg was administered intramuscularly to 18 birds and blood samples were collected via jugular venipuncture at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours after CCFA administration. Plasma concentrations of ceftiofur free acid equivalents (CFAEs) were measured via high-performance liquid chromatography...
December 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/29327947/secnidazole-next-generation-antimicrobial-agent-for-bacterial-vaginosis-treatment
#10
Paul Nyirjesy, Jane R Schwebke
Secnidazole is a next-generation 5-nitroimidazole approved for more than three decades in Europe, Asia, South America and Africa and recently in the USA as a single-dose (2 g) treatment of bacterial vaginosis (BV). Secnidazole is characterized by potent in vitro antimicrobial activity against BV-associated pathogens, as well as prolonged terminal elimination half-life and systemic exposure. These characteristics form the basis of effective and safe treatment of BV with a 2-g single-dose secnidazole regimen, which was recently confirmed in double-blind, placebo-controlled clinical trials conducted in the USA...
January 12, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29326490/investigation-of-in-vitro-absorption-distribution-metabolism-and-excretion-and-in-vivo-pharmacokinetics-of-paromomycin-influence-on-oral-bioavailability
#11
M Jakir S K Pinjari, Rahul Somani, Ritu M Gilhotra
OBJECTIVE: The objective of this study is to investigate in vitro Caco2 permeability, metabolism and in vivo pharmacokinetic (PK) properties of paromomycin to develop an efficient dosage form with improved oral bioavailability. MATERIALS AND METHODS: For the purpose, Caco2 permeability assay, mouse microsomal stability assay and in vivo PKs in male BALB/c mice were performed. RESULTS: In Caco-2 permeability assay, paromomycin showed negligible permeability in the apical to basolateral (A-to-B) direction and vice versa (B-to-A)...
July 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29326081/macromolecule-nanotherapeutics-approaches-and-challenges
#12
REVIEW
Puneet Tyagi, Jose Luis Santos
With the advent of technology, newer forms of drugs, such as proteins, DNA, and RNA, have entered mainstream product development. However, systemic delivery of macromolecules is limited by rapid blood clearance, poor stability in vivo, and inadequate uptake by cells. Nanoparticle (NP)-based delivery systems have emerged as suitable carriers for overcoming such pharmacokinetic limitations of macromolecule delivery. Nanocarriers, such as liposomes, provide protection for sensitive drug materials and also enhance the circulation half-life of=therapeutics...
January 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29325971/incorporation-of-fetal-and-child-pfoa-dosimetry-in-the-derivation-of-health-based-toxicity-values
#13
Kyra Kimberly Kieskamp, Rachel Rogers Worley, Eva D McLanahan, Marc-André Verner
BACKGROUND: Multiple agencies have developed health-based toxicity values for exposure to perfluorooctanoic acid (PFOA). Although PFOA exposure occurs in utero and through breastfeeding, current health-based toxicity values have not been derived using fetal or child dosimetry. Therefore, current values may underestimate the potential risks to fetuses and nursing infants. OBJECTIVE: Using fetal and child dosimetry, we aimed to calculate PFOA maternal human equivalent doses (HEDs), corresponding to a developmental mouse study lowest observed adverse effect level (LOAEL, 1mg/kg/day)...
December 23, 2017: Environment International
https://www.readbyqxmd.com/read/29325724/rheumatoid-arthritis-disease-modifying-agents-and-periprosthetic-joint-infection-what-does-a-joint-surgeon-need-to-know
#14
REVIEW
Mehrnoush H Yeganeh, Michael M Kheir, Alisina Shahi, Javad Parvizi
The incidence of periprosthetic joint infection (PJI) among patients with rheumatoid arthritis (RA) is 1.6× greater than in patients undergoing the same procedure for osteoarthritis. This higher risk "may" be due to the immunosuppressive therapies for RA patients including corticosteroids, such as prednisone, and disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. There is a debate about the role of DMARDs in increasing the incidence of subsequent PJI. Studies show conflicting results, with some demonstrating no significant increase in the rates of PJI and some finding otherwise...
November 23, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/29324626/vascular-effects-of-adrenomedullin-and-the-anti-adrenomedullin-antibody-adrecizumab-in-sepsis
#15
Christopher Geven, Andreas Bergmann, Matthijs Kox, Peter Pickkers
Sepsis remains a major scientific and medical challenge, for which, apart from significant refinements in supportive therapy, treatment has barely changed over the last few decades. During sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock. The free circulating peptide adrenomedullin (ADM) is involved in regulation of the endothelial barrier function and tone of blood vessels. Several animal studies have shown that ADM administration improves outcome of sepsis...
January 10, 2018: Shock
https://www.readbyqxmd.com/read/29324505/when-to-switch-to-an-oral-treatment-and-or-to-discharge-a-patient-with-skin-and-soft-tissue-infections
#16
Matteo Bassetti, Christian Eckmann, Maddalena Peghin, Alessia Carnelutti, Elda Righi
PURPOSE OF REVIEW: Skin and soft tissue infections prevalence is increasing and represent a frequent cause of hospital admission. New guidelines have become available in order to better define these infections and their response to antimicrobial treatment. Gram-positive bacteria, in particular Staphylococcus aureus, remain the most frequently isolated pathogens in skin and soft tissue infections. To treat complicated forms and infections caused by drug-resistant bacteria, hospital admission and administration of intravenous antibiotics are often required, impacting on healthcare costs and patients' morbidity...
January 10, 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29324282/influence-of-glycan-modification-on-igg1-biochemical-and-biophysical-properties
#17
Jake W Pawlowski, Adriana Bajardi-Taccioli, Damian Houde, Marina Feschenko, Tyler Carlage, Igor A Kaltashov
Monoclonal antibodies (mAbs) are the fastest growing class of biopharmaceuticals. The specific therapeutic tasks vary among different mAbs, which may include neutralization of soluble targets, activation of cytotoxic pathways, targeted drug delivery, and diagnostic imaging. The specific therapeutic goal defines which interactions of the antibody with its multiple physiological partners are most critical for function, and which ones are irrelevant or indeed detrimental. In this work, we explored the ability of the glycan chains to affect IgG1 interaction with two key receptor families, FcRn and γ-type Fc receptors, as well as the influence of glycan composition on the conformation and stability of the antibody molecule...
January 3, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29324183/technologies-for-measuring-pharmacokinetic-profiles
#18
A A Heller, S Y Lockwood, T M Janes, D M Spence
The creation of a pharmacokinetic (PK) curve, which follows the plasma concentration of an administered drug as a function of time, is a critical aspect of the drug development process and includes such information as the drug's bioavailability, clearance, and elimination half-life. Prior to a drug of interest gaining clearance for use in human clinical trials, research is performed during the preclinical stages to establish drug safety and dosing metrics from data obtained from the PK studies. Both in vivo animal models and in vitro platforms have limitations in predicting human reaction to a drug due to differences in species and associated simplifications, respectively...
January 11, 2018: Annual Review of Analytical Chemistry
https://www.readbyqxmd.com/read/29322967/alternative-bibliometrics-from-the-web-of-knowledge-surpasses-the-impact-factor-in-a-2-year-ahead-annual-citation-calculation-linear-mixed-design-models-analysis-of-neuroscience-journals
#19
Araceli Diaz-Ruiz, Ulises Orbe-Arteaga, Camilo Rios, Ernesto Roldan-Valadez
CONTEXT: The decision about which journal to choose for the publication of research deserves further investigation. AIMS: In this study, we evaluate the predictive ability of seven bibliometrics in the Web of Knowledge to calculate total cites over a 7-year period in neuroscience journals. SETTINGS AND DESIGN: Coincidental bibliometrics appearing during 2007, 2008, 2009, 2010, and 2011, along with their corresponding cites in 2009, 2010, 2011, 2012, and 2013, were recorded from the journal citation reports (JCR) Science Edition...
January 2018: Neurology India
https://www.readbyqxmd.com/read/29322231/the-effect-of-food-on-the-pharmacokinetics-of-niraparib-a-poly-adp-ribose-polymerase-parp-inhibitor-in-patients-with-recurrent-ovarian-cancer
#20
Kathleen Moore, Zhi-Yi Zhang, Shefali Agarwal, Howard Burris, Manish R Patel, Vikram Kansra
PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. In this open-label crossover study, we evaluated the effects of food on niraparib pharmacokinetics (PK) and safety. METHODS: Patients received a single 300-mg dose of niraparib either after a high-fat meal or under fasting conditions...
January 10, 2018: Cancer Chemotherapy and Pharmacology
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