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Pitavastatin

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https://www.readbyqxmd.com/read/29666154/prediction-and-quantification-of-hepatic-transporter-mediated-uptake-of-pitavastatin-utilizing-a-combination-of-the-relative-activity-factor-approach-and-mechanistic-modeling
#1
Pallabi Mitra, Samantha Weinheimer, Meeghan Michalewicz, Mitchell E Taub
Quantification of the fraction transported (ft) by a particular transporter will facilitate more robust estimations of transporter interactions. Using pitavastatin as a model uptake transporter substrate, we investigated the utility of the relative activity factor (RAF) approach and mechanistic modeling, to estimate ft in hepatocytes. Transporters evaluated were OATP1B1, OATP1B3, and NTCP. Transporter expressing HEK293 cells and human hepatocytes were used for determining RAF values, which were then incorporated into the mechanistic model to simulate hepatocyte uptake of pitavastatin over time...
April 17, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29663259/clinical-investigation-of-coproporphyrins-as-sensitive-biomarkers-to-predict-mild-to-strong-oatp1b-mediated-drug-drug-interactions
#2
Annett Kunze, Emmanuel Njumbe Ediage, Lieve Dillen, Mario Monshouwer, Jan Snoeys
INTRODUCTION: Coproporphyrin (CP) I and III have recently been proposed as endogenous clinical biomarkers to predict organic anion-transporting polypeptide 1B (OATP1B)-mediated drug-drug interactions (DDIs). In the present study, we first investigated the in vitro selectivity of CPI and CPIII towards drug uptake and efflux transporters. We then assessed the in vivo biomarker sensitivity towards OATP1B inhibition. METHODS: To assess transporter selectivity, incubations with CPI and CPIII were performed in vitro, using single transporter-expressing and control systems...
April 16, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29643253/in-vitro-in-vivo-extrapolation-of-oatp1b-mediated-drug-drug-interactions-in-cynomolgus-monkey
#3
Ayse Ufuk, Rachel E Kosa, Hongying Gao, Yi-An Bi, Sweta Modi, Dana Gates, A David Rodrigues, Larry M Tremaine, Manthena V S Varma, J Brian Houston, Aleksandra Galetin
Hepatic organic anion transporting polypeptides (OATP) 1B1 and 1B3 are clinically relevant transporters associated with significant drug-drug interactions (DDIs) and safety concerns. Given that OATP1Bs in cynomolgus monkey share >90% degree of gene and amino acid sequence identity with human orthologs, we evaluated the in vitro-in vivo translation of OATP1B-mediated DDI risk using this preclinical model. In vitro studies using cynomolgus monkey hepatocytes showed active uptake Km values of 2.0 and 3.9 µM for OATP1B probe substrates, pitavastatin and rosuvastatin, respectively...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29626287/suppressive-effect-of-pitavastatin-on-aortic-arch-dilatation-in-acute-stanford-type-b-aortic-dissection-analysis-of-stanp-trial
#4
Naoki Masaki, Kiichiro Kumagai, Konosuke Sasaki, Satoshi Matsuo, Naotaka Motoyoshi, Osamu Adachi, Masatoshi Akiyama, Shunsuke Kawamoto, Koichi Tabayashi, Yoshikatsu Saiki
OBJECTIVES: Medical therapy for patients with uncomplicated acute type B aortic dissection (ABAD) is essentially accepted for its excellent early outcome; however, long-term outcomes have not been satisfactory due to aorta-related complications. This trial was performed to investigate the efficacy of a statin as an additive that may enhance the effectiveness of conventional medical treatment in patients with ABAD. METHODS: This was a multi-center, prospective, and randomized comparative investigation of patients with uncomplicated ABAD...
April 6, 2018: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29574070/duality-of-statin-action-on-lipoprotein-subpopulations-in-the-mixed-dyslipidemia-of-metabolic-syndrome-quantity-vs-quality-over-time-and-implication-of-cetp
#5
M John Chapman, Alexina Orsoni, Paul Robillard, Patrice Therond, Philippe Giral
BACKGROUND: Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. OBJECTIVE: We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. METHODS: Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days...
February 9, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29569046/in-vitro-antibacterial-effects-of-statins-against-bacterial-pathogens-causing-skin-infections
#6
Humphrey H T Ko, Ricky R Lareu, Brett R Dix, Jeffery D Hughes
With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins' antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens...
March 22, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29567347/extrapolation-of-the-hepatic-clearance-of-drugs-in-the-absence-of-albumin-in-vitro-to-that-in-the-presence-of-albumin-in-vivo-comparative-assessement-of-two-extrapolation-models-based-on-the-albumin-mediated-hepatic-uptake-theory-and-limitations-and-mechanistic
#7
Patrick Poulin, Sami Haddad
The extrapolation of hepatic clearance (CL) from data determined in an in vitro assay in the absence of albumin (ALB) to that in the presence of ALB in liver in vivo were often inaccurate using traditional in vitro-to-in vivo extrapolation (IVIVE) methods for drugs binding to the ALB. It is recognized that considering an ALB-facilitated hepatic uptake phenomenon in the IVIVE can improve the extrapolation. Therefore, the present study provides a comparison of two existing models that account for the ALB-facilitated hepatic uptake phenomenon in the IVIVE of CL...
March 19, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29548977/microdosing-cocktail-assay-development-for-drug-drug-interaction-studies
#8
C M Chavez-Eng, R W Lutz, D Goykhman, K P Bateman
Methodology for analysis of a microdosing drug cocktail designed to evaluate the contribution of drug transporters and drug metabolizing enzymes to disposition was developed using LC-MS based detection. Fast and sensitive methods were developed and qualified for the quantification of statins (pitavastatin, pitavastain lactone, rosuvastatin, atorvastatin, 2-hydroxy, and 4-hydroxy atorvastatin), midazolam, and dabigatran in human plasma. Chromatographic separation was accomplished using reversed phase liquid chromatography or HILIC with gradient elution and detection by MS/MS in the positive ionization mode using electrospray ionization...
March 13, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29544396/pitavastatin-treatment-induces-neuroprotection-through-the-bdnf-trkb-signalling-pathway-in-cultured-cerebral-neurons-after-oxygen-glucose-deprivation
#9
Xiaoyan Cui, Zhenqiang Fu, Menghan Wang, Xiaofei Nan, Boai Zhang
OBJECTIVES: Along with their lipid-lowering effect, statins have been reported to have neuroprotective function in both in vivo and in vitro models of neurodegenerative diseases. We conducted this study in order to uncover the he neuroprotective effect of the lipophilic statin pitavastatin (PTV) and investigate the underlying molecular mechanisms using primary cultured cerebral neurons exposed to oxygen-glucose deprivation (OGD). METHODS: The primary cultured cerebral neurons were randomly assigned into four groups: the control group, the pitavastatin treatment group, the OGD group and the OGD + pitavastatin treatment group...
March 16, 2018: Neurological Research
https://www.readbyqxmd.com/read/29522792/differences-in-statin-associated-neuroprotection-corresponds-with-either-decreased-production-of-il-1%C3%AE-or-tnf-%C3%AE-in-an-in-vitro-model-of-neuroinflammation-induced-neurodegeneration
#10
A J McFarland, A K Davey, C M McDermott, G D Grant, J Lewohl, S Anoopkumar-Dukie
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been associated with conflicting effects within the central nervous system (CNS), with underlying mechanisms remaining unclear. Although differences between individual statins' CNS effects have been reported clinically, few studies to date have compared multiple statins' neuroprotective effects. This study aimed to compare six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin; 0-100 μM) using an in vitro model of lipopolysaccharide (LPS)-induced neuroinflammation and subsequent neurodegeneration...
March 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29515050/assessing-impact-of-high-dose-pitavastatin-on-carotid-artery-elasticity-with-speckle-tracking-strain-imaging
#11
Chee Hae Kim, Shuang Wang, Jun-Bean Park, Keun-Hwa Jung, Yeonyee E Yoon, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho, Dae-Won Sohn
AIM: Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity. METHODS: This study was a prospective study including 48 statin-naïve patients (age, 58.2±8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β2 ) were measured using speckle-tracking imaging before and after 3 months of high-dose pitavastatin treatment (4 mg daily)...
March 7, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29503404/rationale-and-design-of-randomized-evaluation-of-aggressive-or-moderate-lipid-lowering-therapy-with-pitavastatin-in-coronary-artery-disease-real-cad-trial
#12
Katsumi Miyauchi, Takeshi Kimura, Hiroaki Shimokawa, Hiroyuki Daida, Satoshi Iimuro, Hiroshi Iwata, Yukio Ozaki, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Seiji Hokimoto, Yasuo Ohashi, Hiroshi Ohtsu, Yasushi Saito, Masunori Matsuzaki, Ryozo Nagai
Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD...
March 5, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29439129/simultaneous-assessment-in-vitro-of-transporter-and-metabolic-processes-in-hepatic-drug-clearance-use-of-a-media-loss-approach
#13
James Harrison, Tom De Bruyn, Adam S Darwich, J Brian Houston
Hepatocyte drug depletion-time assays are well established for the determination of metabolic clearance in vitro. The present study focuses on the refinement and evaluation of a "media loss" assay, an adaptation of the conventional depletion assay involving centrifugation of hepatocytes prior to sampling, allowing estimation of uptake in addition to metabolism. Using experimental procedures consistent with a high throughput, a selection of 12 compounds with a range of uptake and metabolism characteristics (atorvastatin, cerivastatin, clarithromycin, erythromycin, indinavir, pitavastatin, repaglinide, rosuvastatin, saquinavir and valsartan, together with two control compounds - midazolam and tolbutamide) were investigated in the presence and absence of the cytochrome P450 inhibitor 1-aminobenzotriazole and organic anion transporter protein inhibitor rifamycin SV...
February 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29434898/abt-737-and-pictilisib-synergistically-enhance-pitavastatin-induced-apoptosis-in-ovarian-cancer-cells
#14
Elizabeth De Wolf, Christopher De Wolf, Alan Richardson
There is considerable interest in redeploying drugs for use in combination with other oncology therapeutics. The single-agent activity of statins in ovarian cancer has been widely reported, however the drug concentration required to cause cell death is considerably higher than that achieved in patients receiving statin treatment for hypercholesterolemia. Unfortunately, statins can cause myopathy when administered in high doses. One solution to this is to identify drugs that could be used in combination with statins to reduce the dose required and those that may potentially reduce the incidence of adverse side effects...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29427912/adjunctive-therapy-with-statins-in-schizophrenia-patients-a-meta-analysis-and-implications
#15
Hong Shen, Rui Li, Rong Yan, Xia Zhou, Xia Feng, Mengjie Zhao, Hong Xiao
There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis)...
February 5, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29425980/dose-dependent-effects-of-statins-for-patients-with-aneurysmal-subarachnoid-hemorrhage-meta-regression-analysis
#16
REVIEW
Minh-Son To, Shivesh Prakash, Santosh I Poonnoose, Shailesh Bihari
OBJECTIVE: The study utilizes meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DINDs) and mortality in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Prospective, retrospective observational studies and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo)...
February 6, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29404047/electrochemical-determination-of-an-anti-hyperlipidimic-drug-pitavastatin-at-electrochemical-sensor-based-on-electrochemically-pre-treated-polymer-film-modified-gce
#17
Umar J Pandit, Gowhar A Naikoo, Mehraj Ud Din Sheikh, Gulzar A Khan, K K Raj, S N Limaye
An electrochemically pretreated silver macroporous (Ag MP) multiwalled carbon nanotube modified glassy carbon electrode (PAN-Ag MP-MWCNT-GCE) was fabricated for the selective determination of an anti-hyperlipidimic drug, pitavastatin (PST). The fabricated electrochemical sensor was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The fabricated electrode was employed in quantifying and determining PST through differential pulse adsorptive stripping voltammetry (DPAdSV) and CV...
August 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29403315/high-potency-statins-but-not-all-statins-decrease-the-risk-of-new-onset-osteoporotic-fractures-a-nationwide-population-based-longitudinal-cohort-study
#18
Tsung-Kun Lin, Yi-Sheng Liou, Ching-Heng Lin, Pesus Chou, Gwo-Ping Jong
Background: Statins have been linked to new-onset osteoporotic fractures (NOFs), and different statins may alter the risk for the development of NOFs. Aim: In this study, we investigated the association between different statins and the development of NOFs. Patients and methods: This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance, including case patients with NOFs from January 2004 to December 2013 and non-NOF subjects...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29361282/a-rapid-quantitative-assay-for-juvenile-hormones-and-intermediates-in-the-biosynthetic-pathway-using-gas-chromatography-tandem-mass-spectrometry
#19
Zhen-Peng Kai, Yue Yin, Zhi-Ruo Zhang, Juan Huang, Stephen S Tobe, Shan-Shan Chen
A method for rapid quantitation of insect juvenile hormones (JH) and intermediates in the biosynthetic pathway, both in vitro and in vivo (hemolymph and whole body), has been developed using GC-MS/MS. This method is as simple as the radiochemical assay (RCA), the most commonly used method for measurement of JH biosynthesis in vitro, without need for further purification and derivatization, or radioactive precursors or ligands. It shows high sensitivity, accuracy and reproducibility. Linear responses were obtained the range of 1-800 ng/mL (approximately 4-3000 nM)...
February 23, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29344241/combined-pitavastatin-and-dacarbazine-treatment-activates-apoptosis-and-autophagy-resulting-in-synergistic-cytotoxicity-in-melanoma-cells
#20
Abeer Al-Qatati, Saeb Aliwaini
Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death...
December 2017: Oncology Letters
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