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Basic & Clinical Pharmacology & Toxicology

Fadime Canbolat, Dilek Meltem Tasdemir Erinç, Alper Evrensel, Ahmet Aydın, Kaşif Nevzat Tarhan
Therapeutic Drug Monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC-MS/MS to analyse quantitative assay of escitalopram (S-CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S-CT and its metabolites in the patients' plasma...
September 16, 2018: Basic & Clinical Pharmacology & Toxicology
Anna Elgart, Laura Rabinovich, Eli Eyal, Aviva Gross, Ofer Spiegelstein
As of March 2018, rasagiline is approved for the treatment of Parkinson disease in 55 countries including Japan. The present study evaluated the pharmacokinetics (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects following single and multiple administrations of three rasagiline doses. In this double-blind, placebo-controlled study, 64 healthy subjects (32 Japanese and 32 Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10 days with PK sampling for single dose administration on day 1, and for multiple administration on day 10...
September 15, 2018: Basic & Clinical Pharmacology & Toxicology
Tomáš Šálek, Alena Adamíková
The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2 . A total of 265 consecutive T2DM elderly patients (age range 65-91 years) from outpatient diabetic clinic were included in the study...
September 15, 2018: Basic & Clinical Pharmacology & Toxicology
Gail S Prins, Heather B Patisaul, Scott M Belcher, Laura N Vandenberg
Bisphenol A (BPA) is a high-production chemical used in a variety of applications worldwide. While BPA has been documented as an endocrine disrupting chemical (EDC) having adverse health-related outcomes in multiple studies, risk assessment for BPA has lagged due to reliance on guideline toxicology studies over academic ones with endpoints considered more sensitive and appropriate. To address current controversies on BPA safety, the United States National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and the Food and Drug Administration (FDA) established the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) using the NCTR-Sprague-Dawley rats...
September 12, 2018: Basic & Clinical Pharmacology & Toxicology
Flavia Storelli, Jules Desmeules, Youssef Daali
Cytochrome P450 (CYP) 2D6 metabolizes a wide range of xenobiotics and is characterized by a huge inter-individual variability. A recent clinical study highlighted differential magnitude of CYP inhibition as a function of CYP2D6 genotype. The aim of this study was to investigate the effect of CYP2D6 genotype on the inhibition of dextromethorphan O-demethylation by duloxetine and paroxetine in human liver microsomes (HLMs). The study focused on genotypes defined by the combination of two fully functional alleles (activity score 2, AS 2, n=6), of one fully functional and one reduced allele (activity score 1...
September 7, 2018: Basic & Clinical Pharmacology & Toxicology
Priscila A Yamamoto, Jhohann R L Benzi, Francine J Azeredo, Fabíola Dach, Edgar Ianhez Júnior, Cleslei F Zanelli, Natália V de Moraes
Gabapentin (GAB) is eliminated unchanged in urine, and organic cation transporters (OCT2 and OCTN1) have been shown to play a role at GAB renal excretion. This prospective clinical study aimed to evaluate the genetic polymorphisms effect on GAB pharmacokinetic (PK) variability using a population pharmacokinetic approach. Data were collected from fifty-three patients with chronic pain receiving multiple doses of GAB. Patients were genotyped for SLC22A2 c.808G>T and SLC22A4 c.1507C>T polymorphisms. Both polymorphisms' distribution followed the Hardy-Weinberg equilibrium...
September 7, 2018: Basic & Clinical Pharmacology & Toxicology
Xin Liu, Kai Huang, Ziran Niu, Dan Mei, Bo Zhang
Liver fibrosis is a common symptom of non-alcoholic steatohepatitis (NASH) and a worldwide clinical issue. The miR-122/HIF-1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B (ICAB), naturally isolated from Laggera alata, is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine- and choline-deficient (MCD) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg)...
September 4, 2018: Basic & Clinical Pharmacology & Toxicology
Viktoriia Burkina, Martin Krøyer Rasmussen, Yelyzaveta Oliinychenko, Galia Zamaratskaia
Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in humans. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors...
September 1, 2018: Basic & Clinical Pharmacology & Toxicology
Go Wun Choi, Ju-Yeun Lee, Min Jung Chang, Young Kyung Kim, Yoonsook Cho, Yun Mi Yu, Euni Lee
This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato-oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.4 (SD 15.8) years, thrombocytopenia occurred at a rate of 29.2% after an average of 11...
September 1, 2018: Basic & Clinical Pharmacology & Toxicology
Kristina Bram Knudsen, Trine Berthing, Petra Jackson, Sarah Søs Poulsen, Alicja Mortensen, Nicklas Raun Jacobsen, Vidar Skaug, Józef Szarek, Karin Sørig Hougaard, Henrik Wolff, Håkan Wallin, Ulla Vogel
Multi-walled carbon nanotubes (MWCNT) are widely used nanomaterials that cause pulmonary toxicity upon inhalation. The physicochemical properties of MWCNT vary greatly, which makes general safety evaluation challenging to conduct. Identification of the toxicity-inducing physicochemical properties of MWCNT is therefore of great importance. We have evaluated histological changes in lung tissue 1year after a single intratracheal instillation of 11 well-characterized MWCNT in female C57BL/6N BomTac mice. Genotoxicity of liver and spleen was evaluated by the Comet assay...
August 31, 2018: Basic & Clinical Pharmacology & Toxicology
Su Cheol Kim, Myeong Gyu Kim
Uridine 5'-diphospho-glucuronosyltransferases (UGTs) are involved in the metabolism of lamotrigine, but whether the UGT1A4 and UGT2B7 genetic polymorphisms affect lamotrigine concentration remains controversial. Thus, the objective of this meta-analysis was to analyse the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration. Through searching, screening, selection, data extraction and quantitative analyses, the influence of UGT1A4 and UGT2B7 genetic polymorphisms on lamotrigine concentration-to-dose ratio (CDR) was assessed by meta-analysis of nine studies...
August 31, 2018: Basic & Clinical Pharmacology & Toxicology
Magdalena Boncler, Magdalena Lukasiak, Jaroslaw Dastych, Jacek Golanski, Cezary Watala
Mouse 3T3 fibroblasts are commonly used for in vitro toxicity testing; however, their sensitivity to stimuli is not well defined. To assess the sensitivity of the 3T3 cell line, the study compared the changes in mitochondrial membrane potential (MMP) occurring after exposure to eight chemicals known to demonstrate proapoptotic activity (glycerol, isopropanol, ethanol, paracetamol, propranolol, cobalt chloride, formaldehyde and atropine). Five cell lines were used: mouse 3T3 fibroblasts, human epithelial cells (A549, Caco-2, HepG2) and human endothelial cells (HMEC-1)...
August 23, 2018: Basic & Clinical Pharmacology & Toxicology
Seenae Eum, Miyoung Ock, Sera Lee, Hyunah Kim
In this study, clinical manifestations of adverse events and frequently used medications in patients receiving parenteral nutrition (PN) in Korea were evaluated using Korean Adverse Event Reporting System (KAERS) database records between 2011 and 2015. Amino acids, fat emulsions, carbohydrates, combinations and solutions for PN were identified as causative agents. Adverse events classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Centre criteria were analysed...
August 21, 2018: Basic & Clinical Pharmacology & Toxicology
Niva Yacov, Boris Feldman, Alexander Volkov, Eti Ishai, Eyal Breitbart, Itzhak Mendel
Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low-grade inflammation ascribed to toll-like receptor (TLR) activation and monocyte migration. We developed synthetic, small-molecule lecinoxoids, VB-201 and VB-703, that differentially inhibit TLR-2- and TLR-4-mediated activation and monocyte migration. The efficacy of anti-inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model. Five-sixths of nephrectomized rats were treated with lecinoxoids VB-201, VB-703 or PBS, for 7 weeks...
August 20, 2018: Basic & Clinical Pharmacology & Toxicology
Tatiani Botelho Nascimento, Vinícius Bermond Marques, Maylla Ronacher Simões, Patricia Ribeiro do Val Lima, Fabiana Vieira Simões, Dalton Valentim Vassallo, Leonardos Dos Santos
Mercury intoxication is a public health risk factor due to its hazardous effect to several organs, including the cardiovascular system. There is evidence of endothelial dysfunction after exposure to mercury but the effects on endothelium-dependent vasodilatation are still unknown. In the present study, we aimed to evaluate the chronic effects of high HgCl2 doses on the mechanisms of vasodilatation. Wistar rats were injected with HgCl2 (1st dose 10.86 μg/kg, and daily doses 0.014 μg/kg for 30 days i.m.) and saline was used as control...
August 19, 2018: Basic & Clinical Pharmacology & Toxicology
Numan Karaarslan, Ibrahim Yilmaz, Hanefi Ozbek, Duygu Yasar Sirin, Necati Kaplan, Tezcan Caliskan, Cigdem Ozdemir, Yener Akyuva, Ozkan Ates
In the literature, there have been no studies showing clear results on how radio-contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco-molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio-contrast agents...
August 18, 2018: Basic & Clinical Pharmacology & Toxicology
Lingyue Ma, Xiaodan Zhang, Qian Xiang, Shuang Zhou, Nan Zhao, Qiufen Xie, Xia Zhao, Ying Zhou, Yimin Cui
BACKGROUND: The effect of risperidone treatment in patients with schizophrenia varies according to the dopamine receptor genes. This study aimed to evaluate the relationship between genes of the dopamine receptors (D1, D2, and D3) and the effect of risperidone treatment. METHODS: Three electronic databases (PubMed, Embase and Cochrane Library) were searched for relevant cohort or case-control studies published before 9 May 2018. A systematic review and meta-analysis was performed for qualitative and quantitative assessment of the relationship between the dopamine receptors D1, D2 and D3 (DRD1, 2 and 3) and the effect of risperidone treatment...
August 13, 2018: Basic & Clinical Pharmacology & Toxicology
Xiaoye Li, Zi Wang, Qibing Wang, Qing Xu, Qianzhou Lv
Acute coronary syndrome (ACS) has become a vital disease with high mortality worldwide. A combined antiplatelet therapy (aspirin and a P2Y12 antagonist) is commonly used to prevent re-infarction in ACS patients who have undergone percutaneous coronary intervention (PCI). Clopidogrel, a P2Y12 antagonist, plays an important role in the inhibition of platelet aggregation (IPA). However, it is a pro-drug requiring biotransformation by cytochrome P450 (CYP450). The aim of this study is to unravel the effect of clopidogrel-associated genetic variants on inhibition of platelet activity and clinical outcomes in ACS patients...
August 11, 2018: Basic & Clinical Pharmacology & Toxicology
Johannes J van Wattum, Thomas M Leferink, Bob Wilffert, Peter G J Ter Horst
Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling...
July 17, 2018: Basic & Clinical Pharmacology & Toxicology
Hyunah Kim, Seo Yeon Baik, So Jung Yang, Tong Min Kim, Seung-Hwan Lee, Jae Hyoung Cho, In Young Choi, Ju Han Kim, Kun-Ho Yoon, Hun-Sung Kim
Although angiotensin-converting enzyme inhibitor-related angioedema is well known, angiotensin II receptor blocker (ARB)-related angioedema has not been extensively studied because of its lower incidence. Therefore, ARB-related angioedema is likely to be overlooked in the clinical setting. We analysed the medical records of adults who had been prescribed ARB and diagnosed with angioedema between 2009 and 2015. All adults over the age of 18 years who were initially administered ARB between 1 January 2009 and 31 December 2015 were selected as participants in this study...
July 13, 2018: Basic & Clinical Pharmacology & Toxicology
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