journal
MENU ▼
Read by QxMD icon Read
search

Basic & Clinical Pharmacology & Toxicology

journal
https://www.readbyqxmd.com/read/28544774/safety-pharmacokinetics-and-pharmacodynamics-of-hetrombopag-olamine-a-novel-tpo-r-agonist-in-healthy-subjects
#1
Li Zheng, Mao-Zhi Liang, Xiao-Ling Zeng, Cai-Zheng Li, Yi-Fan Zhang, Xiao-Yan Chen, Xi Zhu, An-Bo Xiang
Hetrombopag olamine (hetrombopag) is a novel small-molecule, orally bioavailable, non-peptide thrombopoietin (TPO) receptor agonist that is being developed as the treatment for thrombocytopenia. Two randomized, placebo-controlled phase I studies were conducted in 72 healthy subjects to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of hetrombopag. Hetrombopag was orally administered with a single dose in 5 dose cohorts (5 mg, 10 mg, 20 mg, 30 mg or 40 mg) in the first study, and given once daily for 10 days in 3 dose cohorts (2...
May 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28503840/a-critical-note-on-treatment-of-a-severe-diltiazem-intoxication-high-dose-calcium-and-glucagon-infusions
#2
N M Van Veggel, G J Van der Veen, T C Jansen, E M Westerman
The morbidity and mortality of a severe calcium channel blocker intoxication is high due to serious toxic cardiac effects. Its treatment is supported by low-quality evidence from heterogeneous literature. We describe a case of a severe diltiazem intoxication and critically appraise the efficacy and role of high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the emergency department with a cardiogenic shock with complete AV block, not responding to atropine, isoprenaline and an external pacemaker...
May 15, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28500776/analysis-of-national-pharmacovigilance-data-associated-with-statin-use-in-korea-adverse-drug-reactions-with-statins
#3
Hyunah Kim, Namhyo Kim, Da Hee Lee, Hun-Sung Kim
The aim of this study was to evaluate clinical manifestations, age distribution and risk factors of adverse drug reactions (ADRs) of statins. Korean Adverse Event Reporting System (KAERS) database records (July 2009 - June 2014) on statin-treated adults were used. ADRs classified as "certain," "probable" and "possible" based on the WHO-Uppsala Monitoring Centre criteria were analysed. The frequency of ADRs was compared between adults (18-64 years) and older people (age ≥ 65 years) groups. In total, 2161 ADRs from 1690 patients (579, 34...
May 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28481454/severe-acute-valproic-acid-intoxication-successfully-treated-with-liver-support-therapy
#4
Yongchun Ge, Bin Xu, Chuan Li, Qunpeng He, Tingting Zhu, Rong Fan, Dehua Gong
Valproic acid (VPA) is widely used for treatment of epilepsy. However, its overdose can cause intoxication and could be life-threatening. Due to lack of specific antidote and poorness of endogenous clearance, extracorporeal treatment for severe intoxication cases is indicated. Here, we report a case of severe intoxication of VPA which was successfully treated with liver support therapy. A previously healthy woman was admitted due to coma and hypotension after intentional ingestion of 20 g of sodium valproate...
May 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28481423/the-pig-a-gene-mutation-assay-in-mice-and-human-cells-a-review
#5
Ann-Karin Olsen, Stephen D Dertinger, Christopher T Krüger, Dag M Eide, Christine Instanes, Gunnar Brunborg, Andrea Hartwig, Anne Graupner
This MiniReview describes the principle of mutation assays based on the endogenous Pig-a gene and summarizes results for two species of toxicological interest, mice and humans. The work summarized here largely avoids rat-based studies, as are summarized elsewhere. The Pig-a gene mutation assay has emerged as a valuable tool for quantifying in vivo and in vitro mutational events. The Pig-a locus is located at the X-chromosome, giving the advantage that one inactivated allele can give rise to a mutated phenotype, detectable by multi-colour flow cytometry...
May 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28470941/evolution-of-novel-3d-culture-systems-for-studies-of-human-liver-function-and-assessments-of-the-hepatotoxicity-of-drugs-and-drug-candidates
#6
Tommy B Andersson
The pharmaceutical industry urgently needs reliable pre-clinical models to evaluate the efficacy and safety of new chemical entities before they enter the clinical trials. Development of in vitro model systems that emulate the functions of the human liver organ has been an elusive task. Cell lines exhibit a low drug-metabolizing capacity and primary liver cells rapidly de-differentiate in culture, which restrict their usefulness substantially. Recently, the development of hepatocyte spheroid cultures has shown promising results...
May 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28470827/pharmacogenomics-and-efficacy-of-risperidone-long-term-treatment-in-thai-autistic-children-and-adolescents
#7
Nopphadol Nuntamool, Nattawat Ngamsamut, Natchaya Vanwong, Apichaya Puangpetch, Monpat Chamnanphon, Yaowaluck Hongkaew, Penkhae Limsila, Chuthamanee Suthisisang, Bob Wilffert, Chonlaphat Sukasem
The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcomes in autistic children and adolescents who were treated with risperidone for long periods. Eighty-two autistic subjects diagnosed with DSM-IV and who were treated with risperidone for more than 1 year were recruited. Pharmacogenomics and clinical outcome (CGI-I, aggressive, over-activity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), over-activity (71...
May 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28457021/clinical-effects-of-a-pharmacist-intervention-in-acute-wards-a-randomised-controlled-trial
#8
Trine R H Nielsen, Per H Honoré, Mette Rasmussen, Stig E Andersen
The purpose of the study was to investigate the clinical effect of a clinical pharmacist (CP) intervention upon admission to hospital on in-patient harm and to assess a potential educational bias. Over16 months, 593 adult patients taking ≥ 4 medications daily were included from three Danish acute medicine wards. Patients were randomised to 'either the CP intervention or the usual care (prospective control). To assess a potential educational bias or educational bias, a retrospective control group was formed by randomisation...
April 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28444983/azilsartan-medoxomil-an-angiotensin-ii-receptor-antagonist-for-the-treatment-of-hypertension
#9
Marie Harthøj Hjermitslev, Daniela Grimm, Markus Wehland, Ulf Simonsen, Marcus Krüger
Azilsartan medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin-II receptor blockers (ARBs) that have been on the market for a longer period. This article is protected by copyright. All rights reserved.
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28444958/role-of-cytochrome-p450-3a4-and-1a2-phenotyping-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-receiving-erlotinib-treatment
#10
Zinnia P Parra-Guillen, Peter B Berger, Manuel Haschke, Massimiliano Donzelli, Daria Winogradova, Bogumila Pfister, Martin Früh, Charlotte Kloft, Stephan Krähenbühl, Silke Gillessen, Markus Joerger
Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD. was initiated, and the 2 oral probe drugs midazolam (2mg) and caffeine (100mg) were added on day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for up to 6 hr on day 1 and 2-weekly up to week 10...
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28437032/autonomic-receptor-mediated-regulation-of-production-and-release-of-nitric-oxide-in-normal-and-malignant-human-urothelial-cells
#11
Michael Winder, Renata Vesela, Patrik Aronsson, Bhavik Patel, Thomas Carlsson
In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines - the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and western blotting...
April 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28429887/effects-of-aluminium-on-long-term-memory-in-rats-and-on-sirt1-mediating-the-transcription-of-creb-dependent-gene-in-hippocampus
#12
Dongying Yan, Cuihong Jin, Yang Cao, Lulu Wang, Xiaobo Lu, Jinghua Yang, Shengwen Wu, Yuan Cai
Epidemiological investigations have shown that aluminium (Al) is an important neurotoxicant which can be absorbed by organisms via various routes. Previous studies have confirmed that exposure to Al could cause neurodegenerative diseases, decline CREB phosphorylation and then down-regulate the transcription and protein expression of its target genes including BDNF. However, recent studies revealed that CREB activation alone was far from enough to activate the expression of long-term memory (LTM) related genes; there might be other regulatory factors involved in this process...
April 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28419737/a-10-year-experience-of-therapeutic-drug-monitoring-tdm-of-linezolid-in-a-hospital-wide-population-of-patients-receiving-conventional-dosing-is-there-enough-evidence-for-suggesting-tdm-in-the-majority-of-patients
#13
Federico Pea, Pier Giorgio Cojutti, Massimo Baraldo
A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (Cmin ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of Cmin was set between 2 and 7 mg/L (under-exposure, Cmin < 2 mg/L; over-exposure, Cmin > 7 mg/L)...
April 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28397349/therapeutic-drug-monitoring-of-venlafaxine-in-an-everyday-clinical-setting-analysis-of-age-sex-and-dose-concentration-relationships
#14
Morten Rix Hansen, Ida Berglund Kuhlmann, Anton Pottegård, Per Damkier
Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1,077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg...
April 11, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374982/angiotensin-ii-receptor-blockers-inhibit-the-generation-of-epoxyeicosatrienoic-acid-from-arachidonic-acid-in-recombinant-cyp2c9-cyp2j2-and-human-liver-microsomes
#15
Asuna Senda, Yuji Mukai, Toru Hayakawa, Yuka Kato, Erik Eliasson, Anders Rane, Takaki Toda, Nobuo Inotsume
Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), have cardioprotective effects including anti-inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2, and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC50 ) of AA metabolism was losartan < telmisartan < irbesartan < candesartan < olmesartan < valsartan via CYP2C9, and telmisartan < irbesartan < olmesartan < losartan < candesartan and valsartan via CYP2J2...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374979/matrix-metalloproteinase-mmp-2-activity-is-associated-with-divergent-regulation-of-calponin-1-in-conductance-and-resistance-arteries-in-hypertension-induced-early-vascular-dysfunction-and-remodelling
#16
Juliana M Parente, Camila A Pereira, Gustavo H Oliveira-Paula, José Eduardo Tanus-Santos, Rita C Tostes, Michele M Castro
Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMC) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374976/ppar%C3%AE-activation-suppresses-cytochrome-p450-induction-potential-in-mice-treated-with-gemfibrozil
#17
Cunzhong Shi, Luo Min, Julin Yang, Manyun Dai, Danjun Song, Huiying Hua, Gangming Xu, Frank J Gonzalez, Aiming Liu
Gemfibrozil, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely used for hypertriglyceridaemia and mixed hyperlipidaemia. Drug-drug interaction of gemfibrozil and other PPARα agonists has been reported. However, the role of PPARα in Cytochrome P450 (CYP) induction by fibrates is not well known. In this study, wild-type mice were first fed gemfibrozil-containing diets (0.375%, 0.75% and 1.5%) for 14 days to establish a dose-response relationship for CYP induction. Then, wild-type mice and Pparα-null mice were treated with a 0...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374975/enrichment-of-genetic-variants-in-the-glucocorticoid-receptor-signalling-pathway-in-autoimmune-hepatitis-with-failure-of-standard-treatment
#18
Peter Lykke Eriksen, Martin Kreutzfeldt, Henning Grønbaek, Kasper Thorsen, Søren Vang, Niels Jessen, Hendrik Vilstrup
The standard treatment for autoimmune hepatitis (AIH) is predniso(lo)ne for remission induction, tapered and followed by azathioprine, which effectively controls the disease in the majority of patients. However, some patients prove to be unresponsive or non-tolerant and require alternative immunosuppressive regimens for disease control. We aimed to investigate whether these AIH patients who experience failure of standard treatment have a genomic basis for their problem in the form of pharmacogenetic variants...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374974/mathematical-modelling-of-glucose-dependent-insulinotropic-polypeptide-and-glucagon-like-peptide-1-following-ingestion-of-glucose
#19
Rikke M Røge, Jonatan I Bagger, Oskar Alskär, Niels R Kristensen, Søren Klim, Jens J Holst, Steen H Ingwersen, Mats O Karlsson, Filip K Knop, Tina Vilsbøll, Maria C Kjellsson
The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting glucagon secretion and delaying gastric emptying. As the insulinotropic effect of GLP-1 is preserved in patients with type 2 diabetes (T2D), therapies based on GLP-1 have been developed in recent years, and these have proven to be efficient in the treatment of T2D...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28374970/human-bj-fibroblasts-is-an-alternative-to-mouse-balb-c-3t3-cells-in-in-vitro-neutral-red-uptake-assay
#20
Marika Mannerström, Tarja Toimela, Jertta-Riina Sarkanen, Tuula Heinonen
The OECD GD 129 BALB/c 3T3 Neutral Red Uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human relevant cytotoxicity data, we performed an intra-laboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
journal
journal
40644
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"