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Basic & Clinical Pharmacology & Toxicology

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https://read.qxmd.com/read/30739396/physiologically-based-pharmacokinetic-modelling-to-predict-exposure-differences-in-healthy-volunteers-and-subjects-with-renal-impairment-ceftazidime-case-study
#1
Li Zhou, Xiao Tong, Pradeep Sharma, Hongmei Xu, Nidal Al-Huniti, Diansong Zhou
Ceftazidime is a widely used β-lactam antibiotic and almost entirely excreted via glomerular filtration in kidney. The objective of this analysis was to assess the ability of physiologically-based pharmacokinetic (PBPK) model to predict ceftazidime exposure in healthy volunteers and subjects with renal impairment. A full PBPK model of ceftazidime was developed using physiochemical properties and clinical data. The total clearance of 115 mL/min and renal clearance of 100 mL/min were obtained from ceftazidime package insert...
February 9, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30739389/management-of-pharmacotherapy-related-problems-in-acute-coronary-syndrome-role-of-clinical-pharmacist-in-cardiac-rehabilitation-unit
#2
Eman Ahmed Casper, Lamiaa Mohmed El Wakeel, Mohamed Ayman Saleh, Manal Hamed El-Hamamsy
Acute coronary syndrome (ACS) is one of the leading causes of mortality worldwide and negatively impacts health care costs, productivity and quality of life. Poly-morbidity and poly-pharmacy predispose ACS patients to medication discrepancies between cardiologist-prescribed medication and drug use by the patient, drug-related problems (DRPs) and inadequate drug adherence. This study aimed to evaluate the impact of clinical pharmacist-provided services on the outcome of ACS patients. This was a prospective, randomised, controlled study on ACS patients participating in a cardiac rehabilitation program...
February 9, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30715804/identifying-factors-affecting-the-pharmacokinetics-of-voriconazole-in-patients-with-liver-dysfunction-a-population-pharmacokinetic-approach
#3
Dan Tang, Bai-Li Song, Miao Yan, Jian-Jun Zou, Min Zhang, Hua-Ying Zhou, Feng Wang, Yi-Wen Xiao, Ping Xu, Bi-Kui Zhang, Xi-Jing Chen, Da-Xiong Xiang, Hoan Linh Banh
Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction, and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study...
February 4, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30712291/adjuvant-potential-of-selegiline-in-treating-acute-toxicity-of-aluminium-phosphide-in-rats
#4
Adeleh Maleki, Mir-Jamal Hosseini, Nastaran Rahimi, Alireza Abdollahi, Amir Akbarfakhrabadi, Nina Javadian, Shayan Amiri, Behnam Behnoush, Ahmad Reza Dehpour
Aluminium phosphide (AlP); is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status, and electrocardiographic parameters in rats following AlP poisoning...
February 3, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30697954/upregulation-of-rac1-in-the-bronchial-smooth-muscle-of-murine-experimental-asthma
#5
Yuki Kai, Momoko Motegi, Yuta Suzuki, Hiroto Takeuchi, Yui Harada, Fumiaki Sato, Yoshihiko Chiba, Junzo Kamei, Hiroyasu Sakai
There has been considerable research on the involvement of RhoA/Rho kinase signalling in smooth muscle contractions. However, only a few reports have addressed the specific role of Rac1, which is a member of the Rho GTPase superfamily. Therefore, this study investigated the role of Rac1-related pathways in bronchial smooth muscle (BSM) contractions. Bronchial rings isolated from mice were suspended in an organ bath, and the isometric contractions of circular smooth muscles were monitored. The phosphorylation of myosin light chains (MLCs) was analysed by immunoblotting...
January 29, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30694600/short-course-versus-long-course-antibiotic-treatment-for-community-acquired-pneumonia-a-literature-review
#6
Kamilla Møller Gundersen, Jette Nygaard Jensen, Lars Bjerrum, Malene Plejdrup Hansen
BACKGROUND: It is well known that antibiotic use is the main driver for the increasing problems with resistant bacteria. Consequently, some countries have recommended shortening the duration of antibiotic treatment of community-acquired pneumonia (CAP). The aim of this study was to investigate if the effectiveness of a short-course antibiotic is comparable to a longer course of antibiotics in adults with CAP and to assess if the duration of an antibiotic course influences the development of resistant bacteria...
January 29, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30694594/midd0301-a-first-in-class-anti-inflammatory-asthma-drug-targets-gaba-a-receptors-without-causing-systemic-immune-suppression
#7
Nicolas M Zahn, Alec T Huber, Brandon Nicholas Mikulsky, Mae Elizabeth Stepanski, Alexander Scott Kehoe, Guanguan Li, Melissa Schussman, M S Rashid Roni, Revathi Kodali, James M Cook, Douglas C Stafford, Douglas A Steeber, Leggy A Arnold
We report a 28-day repeat dose immunotoxicity evaluation of investigational drug MIDD0301, a novel oral asthma drug candidate that targets gamma amino butyric acid type A receptors (GABAA R) in the lung. The study design employed oral administration of mice twice daily throughout the study period with 100 mg/kg MIDD0301 mixed in peanut butter. Compound dosing did not reveal signs of general toxicity as determined by animal weight, organ weight, or hematology. Peanut butter plus test drug (in addition to ad libitum standard rodent chow) did not affect weight gain in the adult mice, in contrast to weight loss in 5 mg/kg prednisone-treated mice...
January 29, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30681278/lamotrigine-drug-interactions-in-combination-therapy-and-the-influence-of-therapeutic-drug-monitoring-on-clinical-outcomes-in-paediatric-patients
#8
Blanka Koristkova, Milan Grundmann, Hana Brozmanova, Ivana Kacirova
The aim was to study the impact of therapeutic drug monitoring (TDM) on paediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. During the period of 2001-2015, 1308 pre-dose samples were taken from 430 patients <15 years of age as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Valproic acid decreased lamotrigine clearance by 54% in bitherapy, and by 21% in triple therapy with carbamazepine...
January 25, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30672131/progression-free-survival-pfs-in-oncology-caveat-emptor
#9
LETTER
Sinan B Sarac, Mark A Ainsworth, Doris Hovgaard, Ole W Bjerrum
No abstract text is available yet for this article.
January 22, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30661290/population-pharmacokinetics-of-brodalumab-in-patients-with-moderate-to-severe-plaque-psoriasis
#10
Stine Timmermann, Anders Hall
Brodalumab is a fully human monoclonal antibody targeting the IL-17 receptor A leading to an inhibition of the biological effect of IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E isoforms. It has shown to be efficacious in the treatment of moderate to severe plaque psoriasis (210 mg administered subcutaneously at weeks 0, 1 and 2 followed by 210 mg every 2 weeks (Q2W+1)). A population pharmacokinetic model based on psoriasis patients only from 6 clinical trials was developed to describe the pharmacokinetics and identify sources of variability...
January 20, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30624861/myricetin-inhibits-panel-of-kinases-implicated-in-tumorigenesis
#11
Stefani Stoll, Shanna Bitencourt, Stefan Laufer, Márcia Goettert
About 80% of the antineoplastic drugs produced in the last 30 years are of natural origin or their derivatives, evidencing the great contribution of natural products in the development of new drugs (1). Phytochemical constituents of various plants are a source of biomolecules candidates (2), including polyphenols as flavonoids, showing expressive antioxidant (3, 4) and anticancer features (5). Flavonoids constituents are known for their antitumour activity such as inhibition of cell proliferation, adhesion and invasion, cell cycle arrest and apoptosis (6)...
January 9, 2019: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30589994/pharmacokinetics-pharmacodynamics-tolerability-and-prediction-of-clinically-effective-dose-of-act-774312-a-novel-crth2-antagonist
#12
Martine Géhin, Dominik Lott, Hervé Farine, Milena Issac, Daniel Strasser, Patricia Sidharta, Jasper Dingemanse
ACT-774312 is an antagonist of the chemoattractant receptor-homologous molecule expressed on T helper (Th) 2 cells (CRTH2), in development for the treatment of nasal polyposis or other allergic and type-2 inflammatory diseases. Placebo, single doses of 1 to 1000 mg, or multiple doses of 30 to 500 mg either once or twice daily for 4 days of ACT-774312 were administered orally to healthy subjects. The single- and multiple-dose pharmacokinetics of ACT-774312 were dose-proportional and characterized by a time to attainment of maximum plasma concentrations between 1 and 3 hr and a terminal elimination half-life of about 12 hr...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30589992/cross-national-comparison-of-paediatric-antibiotic-use-in-norway-portugal-and-hungary
#13
Ria Benko, Maria Matuz, Ana Silva, Joaquina Ferreira, Maria Céu Machado, Cláudia Furtado, Githa Fungie, Reka Bordas, Hege Salvesen Blix
A cross-national comparison was performed on paediatric (0-19 years) antibiotic use in Hungary, Norway and Portugal to explore and compare the scale and pattern of paediatric antibiotic use in these three European countries. Ambulatory care systemic antibiotic use (ATC: J01) was retrieved from national databases for year 2014. The main outcome measure was number of antibacterial packages per child inhabitant per year (packages/child/year) and was further stratified by age groups. Paediatric antibiotic use peaked in Hungary with 1...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30589990/pharmacogenomics-research-and-clinical-implementation-in-brazil
#14
Fernanda Rodrigues-Soares, Guilherme Suarez-Kurtz
We searched Pubmed entries and the Lattes database for Brazilian Pharmacogenetics Network investigators, for pharmacogenetic/genomic (PGx) studies in the Brazilian population, focusing on the drugs and genes included in the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Warfarin was the most extensively studied drug in a PGx context: a Genome-Wide Association Study targeting warfarin stable dose identified significant signals in VKORC1 and CYP2C9, several PGx dosing algorithms were developed based on these and other genes, and the implications of population admixture on extrapolation of dosing recommendations in the CPIC guidelines were examined...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30589220/flaws-in-design-execution-and-interpretation-limit-clarity-bpa-s-value-for-risk-assessments-of-bisphenol-a
#15
Frederick S Vom Saal
The Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) involved the Food and Drug Administration, the National Toxicology Program and 14 academic investigators funded by the National Institute of Environmental Health Sciences. Two key questions to be answered by CLARITY-BPA were: 1. Would the academic investigator studies show effects at low doses of BPA while the core guideline study conducted by the FDA only showed toxic effects at high doses? 2. Would the academic investigators be able to replicate their numerous prior studies with animals raised and treated in the FDA's toxicology centre? Several flaws in the design and execution of CLARITY-BPA biased the experiment toward not finding significant results (Type 2 error): 1...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30589214/neurotoxic-effects-of-mercury-exposure-in-dental-personnel
#16
Geir Bjørklund, Bjørn Hilt, Maryam Dadar, Ulf Lindh, Jan Aaseth
Numerous studies have reported neurobehavioural effects in dental personnel occupationally exposed to chronic low levels of mercury (Hg). Mercury exposure from dental work may also induce various chronic conditions such as elevation of amyloid protein expression, deterioration of microtubules, and increase or inhibition of transmitter release at motor nerve terminal endings. Therefore, clinical studies of Hg toxicity in dentistry may provide new knowledge about disturbed metal homeostasis in neurodegenerative diseases like Alzheimer's disease, multiple sclerosis and mood disorders...
December 27, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30561898/stevioside-inhibits-experimental-fibrosis-by-down-regulating-profibrotic-smad-pathways-and-blocking-hepatic-stellate-cell-activation
#17
Sael Casas-Grajales, Diana Alvarez-Suarez, Erika Ramos-Tovar, Laura Dayana Buendía-Montaño, Karina Reyes-Gordillo, Javier Camacho, Víctor Tsutsumi, M Raj Lakshman, Pablo Muriel
Liver cirrhosis is associated with increased morbidity and mortality with important health and social consequences; however, an effective treatment has not been found yet. Previous reports have shown some beneficial effects of stevioside (SVT) in different diseases, but the ability of SVT to inhibit liver cirrhosis has not been reported. Therefore, we studied the potential of this diterpenoid to inhibit liver cirrhosis induced by thioacetamide, a model that shares many similarities with the human disease, and investigated the possible underlying molecular mechanism using in vivo and in vitro approaches...
December 18, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30561843/nordic-symposium-on-toxicology-and-pharmacology-without-animal-experiments-will-it-be-possible-in-the-next-10-years
#18
Lisbeth E Knudsen, Adrian Smith, Elin Törnqvist, Anna Forsby, Hanna Tähti
Toxicological and pharmacological information from human cells and tissues provides knowledge readily applicable to human safety assessment and to the efficacy assessment of pharmaceuticals. The 3R principle in animal studies includes the use of human material in the R of Replacement. The Reduction and Refinement Rs are related to animal use. Knowledge of the 3Rs and successful 3R methods are a prerequisite for the reduction of animal experiments in the future. More collaboration among researchers using experimental animals and those working in vitro is necessary with mutual respect...
December 18, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30561132/a-role-of-peroxisome-proliferator-activated-receptor-%C3%AE-in-non-alcoholic-fatty-liver-disease
#19
Josephine Skat-Rørdam, David Højland Ipsen, Jens Lykkesfeldt, Pernille Tveden-Nyborg
Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and have been investigated in several clinical trials for their potential in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). PPARγ has specialized roles in distinct tissues and cell types, and although the primary function of PPARγ is in adipose tissue, where the highest expression levels are observed, hepatic expression levels of PPARγ are significantly increased in patients with NAFLD...
December 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://read.qxmd.com/read/30556952/use-of-proton-pump-inhibitors-among-danish-children-a-16-year-register-based-nationwide-study
#20
Ignacio Aznar-Lou, Mette Reilev, Anders Bergh Lødrup, Maria Rubio-Valera, Peter Fentz Haastrup, Anton Pottegård
OBJECTIVES: Proton pump inhibitors (PPI) are among the most frequently used drugs in the developed countries. In recent years, their use among children and adolescents has been on the increase. Guidelines recommend use for a period no longer than 4-8 weeks. The aim of this study was to describe time trends in prescribing patterns of PPI use among children, with emphasis on persistence to therapy. METHODS: We used the Danish nationwide healthcare registries and identified all Danish children (0-17 years old) who were provided with a filled in PPI prescription between 2000 and 2015...
December 17, 2018: Basic & Clinical Pharmacology & Toxicology
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