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statins with time of dosing

Yewon Choi, SeungHwan Lee, In-Jin Jang, Kyung-Sang Yu
Introduction: Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). The study's objective was to evaluate the effect of coadministration of fimasartan and atorvastatin on their pharmacokinetics (PKs). Subjects and methods: In a randomized, open-label, three-period, six-sequence, crossover, multiple-dose study, 36 healthy subjects received 120 mg fimasartan, 40 mg atorvastatin, or both (based on their assigned sequence) once daily for 7 days in each period, with a 7-day washout between periods...
2018: Drug Design, Development and Therapy
Tamara R Nikolic Turnic, Vladimir Jakovljevic, Dragan Djuric, Nevena Jeremic, Jovana Jeremic, Isidora Milosavljevic, Ivan M Srejovic, Dragica Selakovic, Vladimir I Zivkovic
The aim of this study was to assess impact of atorvastain and simvastatin on myocardial contractility during the different degree of Hhcy in rats. Study was conducted on adult male Wistar albino rats (n=96; 4 weeks old; 100±15g body mass) in which HHcy was achieved by dietary manipulation. Animals were exposed to pharmacology treatment with atorvastatin in dose of 3 mg/kg/day i.p or simvastatin in dose of 5 mg/kg/day i.p in same time every day, according to equivalent therapeutic doses of these statins (10mg atorvastatin=20mg simvastatin)...
August 1, 2018: Canadian Journal of Physiology and Pharmacology
Florine Tissier, Firas Farhat, Clothilde Philouze, Jean-Claude Desfontis, Romain Didier, Martine Gilard, M Yassine Mallem, Jacques Mansourati, Christine Moisan, Karine PIchavant-Rafini, Michael Theron, Aline Amérand
Statins are currently used in prevention of cardiovascular diseases in high risk populations, and could be considered in primary prevention. However, few studies are available on the long-term effects of low-doses of statins, especially on mitochondrial function and ROS (Reactive Oxygen Species) metabolism at cardiac level. This study aimed to determine potential effects of a long-term atorvastatin treatment, at low-dose concentration, on the myocardium mitochondrial respiration. 34 Watanabe rabbits were treated or not with atorvastatin (2...
July 16, 2018: Canadian Journal of Physiology and Pharmacology
Junyu Zhao, Chunmei Xu, Jinming Yao, Changzhen Yu, Lin Liao, Jianjun Dong
BACKGROUND/AIMS: Experimental studies have reported the antineoplastic effects of statins in thyroid carcinoma; however, observational studies suggested that statins might increase the risk of thyroid carcinoma. Therefore, this study evaluated the antineoplastic effects of statins in both in vitro studies and animal models, as well as the epidemiological evidence. METHODS: Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries- were searched...
June 19, 2018: Cellular Physiology and Biochemistry
Gaetano M De Ferrari, Gian P Perna, Antonino Nicosia, Luigina Guasti, Gavino Casu, Claudio Cuccia, Francesca Picco, Caterina Strazzella, Rossana Totaro, Stefania Cercone, Laura Canullo, Martin Horack, Dominik Lautsch, Anselm K Gitt, Matteo Di Biase
AIMS: The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe. METHODS: The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile...
June 18, 2018: Journal of Cardiovascular Medicine
E O Vershinina, A N Repin, M S Timofeev, V V Udut
PURPOSE OF THE STUDY: To compare the effect of loading doses of atorvastatin and rosuvastatin on the value of the acute kidney injury and acute inflammatory response to elective percutaneous coronary interventions. MATERIALS AND METHODS: An open prospective comparative study included 68 patients referred for elective percutaneous coronary intervention (PCI). At baseline, all patients had been taking statins for a long time as a standard lipid-lowering therapy. The first group included 33 patients who received a loading dose of 80 mg of atorvastatin (As) 12 hours before the intervention with saving this dose for 2-6 days...
2018: Kardiologiia
Susana Barros, Rosa Montes, José Benito Quintana, Rosario Rodil, Ana André, Ana Capitão, Joana Soares, Miguel M Santos, Teresa Neuparth
Simvastatin (SIM), a hypocholesterolaemic compound, is among the most prescribed pharmaceuticals for cardiovascular disease prevention worldwide. Several studies have shown that acute exposure to SIM causes multiple adverse effects in aquatic organisms. However, uncertainties still remain regarding the chronic effects of SIM in aquatic ecosystems. Therefore, the present study aimed to investigate the effects of SIM in the model freshwater teleost zebrafish (Danio rerio) following a chronic exposure (90 days) to environmentally relevant concentrations ranging from 8 ng/L to 1000 ng/L...
May 25, 2018: Aquatic Toxicology
Joël Coste, Cécile Billionnet, Annie Rudnichi, Jacques Pouchot, Rosemary Dray-Spira, Philippe Giral, Mahmoud Zureik
Aims The purpose of this study was to investigate the risk of rhabdomyolysis in subjects initiating statin therapy for primary prevention of cardiovascular disease, focusing on the type of statin, dose and time since initiation. Methods and results A nationwide cohort study using French hospital discharge and claims databases was performed, studying subjects from the general population 40-75 years in 2009, with no history of cardiovascular disease and no lipid-lowering drugs during the preceding three-year period, followed for up to seven years...
January 1, 2018: European Journal of Preventive Cardiology
Kamal Awad, Maciej Banach
PURPOSE OF REVIEW: In humans, cholesterol biosynthesis varies diurnally, reaching its peak at night. Therefore, choosing the time of statin administration is critical because of their different half-lives. Dose timing becomes more important in patients with polypharmacy because it might affect their adherence to the statin therapy. RECENT FINDINGS: Herein, we narratively summarized the available clinical studies (n = 17) and meta-analyses (n = 2) that compared the morning with the evening dose of statins in terms of safety and efficacy, with special focus on their low-density lipoprotein-lowering effects...
August 2018: Current Opinion in Lipidology
Peter Ihle, Franz-Werner Dippel, Ingrid Schubert
Aim of the study was to assess the incidence of statin-associated myopathy (SAM) under real-life conditions in Germany. DATABASE: Administrative data (master data, diagnoses, prescriptions) for all individuals in Germany insured with the Statutory Health Insurance. Basic population: individuals 18 years and older who have been insured continually from 2009 to 2011 (52.9 million; 29.9 million men, 23.9 million women). Data access is provided by the German Institute of Medical Documentation and Information, DIMDI) according to the Data Transparency Regulation of 2012...
June 2018: Pharmacology Research & Perspectives
Samira Salihovic, Jordan Stubleski, Anna Kärrman, Anders Larsson, Tove Fall, Lars Lind, P Monica Lind
BACKGROUND: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent. OBJECTIVE: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data. METHODS: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS)...
August 2018: Environment International
Ye Sel Kim, Moo-Seok Park, Jun-Hwa Lee, Jong-Won Chung, Mi Ji Lee, Chi Kyung Kim, Jin-Man Jung, Kyungmi Oh, Oh Young Bang, Geong-Moon Kim, Ji-Mi Choi, Juneyoung Lee, Chin Sang Chung, Kwang Ho Lee, Woo-Keun Seo
The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality...
2018: Frontiers in Neurology
Kausik K Ray, Robert M Stoekenbroek, David Kallend, Lawrence A Leiter, Ulf Landmesser, R Scott Wright, Peter Wijngaard, John J Kastelein
Background -The ORION-1 trial demonstrated that inclisiran, a small interfering RNA (siRNA) therapeutic that targets PCSK9 mRNA within hepatocytes, produces significant LDL-C reduction. The effects of inclisiran on other lipids are less well described. Methods -ORION-1 was a phase 2 trial assessing 6 different inclisiran dosing regimens vs placebo. Participants with elevated LDL-C despite receiving maximally tolerated statin therapy received a single- (200, 300 or 500mg) or two-dose starting regimen (100, 200 or 300mg on days 1 and 90) of inclisiran or placebo...
May 7, 2018: Circulation
Xavier Nicolas, Nassim Djebli, Clémence Rauch, Aurélie Brunet, Fabrice Hurbin, Jean-Marie Martinez, David Fabre
BACKGROUND: Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. OBJECTIVE: This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. METHODS: From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations...
May 3, 2018: Clinical Pharmacokinetics
Jean-Marie Martinez, Aurélie Brunet, Fabrice Hurbin, A Thomas DiCioccio, Clémence Rauch, David Fabre
BACKGROUND: Alirocumab, a human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) to significantly reduce low-density lipoprotein cholesterol levels; pharmacokinetics (PK) are governed by non-linear, target-mediated drug disposition (TMDD). OBJECTIVES: We aimed to develop and qualify a population PK (PopPK) model to characterize the PK profile of alirocumab, evaluate the impact of covariates on alirocumab PK and on individual patient exposures, and estimate individual predicted concentrations for a subsequent PK/pharmacodynamic (PD) analysis...
May 3, 2018: Clinical Pharmacokinetics
Nijole Bernaitis, Chi Keong Ching, Siew Chong Teo, Tony Badrick, Andrew K Davey, Julia Crilly, Shailendra Anoopkumar-Dukie
BACKGROUND: Warfarin requires ongoing monitoring of the International Normalised Ratio (INR). This is because numerous factors influence the response, including drug interactions with commonly-prescribed medications, such as statins. The administration of statins with warfarin may change INR; however, there is limited information regarding the effects on warfarin control as measured by time in therapeutic range (TTR). Statins may also alter bleeds with warfarin, but there are conflicting reports demonstrating both increased and decreased bleeds, and limited data on diverse ethnic populations...
May 1, 2018: Journal of Clinical Medicine
Hung-Wei Lin, Yunn-Fang Ho, Fang-Ju Lin
AIMS: To examine the association between statin use before and after intracranial haemorrhage (ICH) and the risk of poststroke epilepsy (PSE). METHODS: Patients with new-onset ICH between 2004 and 2012 were identified from the Taiwan National Health Insurance Research Database. The main outcome was the occurrence of epilepsy after stroke. Multivariable Cox regression modelling was used to estimate the association between statin use and the risk of PSE, with poststroke medication exposures being treated as time-dependent variables...
May 1, 2018: British Journal of Clinical Pharmacology
Jatinder S Minhas, Xia Wang, Hisatomi Arima, Philip M Bath, Laurent Billot, Joseph P Broderick, Geoffrey A Donnan, Jong S Kim, Pablo M Lavados, Tsong-Hai Lee, Sheila Cristina Ouriques Martins, Verónica V Olavarría, Jeyaraj D Pandian, Octávio Marques Pontes-Neto, Stefano Ricci, Shoichiro Sato, Vijay K Sharma, Nguyen H Thang, Ji-Guang Wang, Mark Woodward, John Chalmers, Craig S Anderson, Thompson G Robinson
BACKGROUND: Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup -analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. METHODS: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66...
April 27, 2018: Cerebrovascular Diseases
Jieon Lee, Su-Jin Rhee, SeungHwan Lee, Kyung-Sang Yu
Objectives: As hypercholesterolemia is often accompanied by hypertension, statins are usually prescribed with angiotensin receptor blockers in clinical practice. This study was performed to evaluate the pharmacokinetics and safety of fimasartan and rosuvastatin when coadministered or administered alone as a single dose or as multiple doses to healthy Caucasians. Methods: Thirty-six subjects were enrolled into an open-labeled, randomized, 6-sequence, 3-period, 3-way crossover study, and randomly received fimasartan (120 mg), rosuvastatin (20 mg) or both...
2018: Drug Design, Development and Therapy
Fang-Ju Lin, Hung-Wei Lin, Yunn-Fang Ho
BACKGROUND: Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. OBJECTIVE: The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013). METHODS: Patients with new-onset ischaemic stroke were identified...
April 2018: CNS Drugs
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