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The limited number of antifungals and the rising frequency of azole-resistant Candida species are growing challenges to human medicine. Drug repurposing signifies an appealing approach to enhance the activity of current antifungal drugs. Here, we evaluated the ability of Pharmakon 1600 drug library to sensitize an azole-resistant Candida albicans to the effect of fluconazole. The primary screen revealed 44 non-antifungal hits were able to act synergistically with fluconazole against the test strain. Of note, 21 compounds, showed aptness for systemic administration and limited toxic effects, were considered as potential fluconazole adjuvants and thus were termed as "repositionable hits". A follow-up analysis revealed pitavastatin displaying the most potent fluconazole chemosensitizing activity against the test strain (ΣFICI 0.05) and thus was further evaluated against 18 isolates of C. albicans (n = 9), C. glabrata (n = 4), and C. auris (n = 5). Pitavastatin displayed broad-spectrum synergistic interactions with both fluconazole and voriconazole against ~89% of the tested strains (ΣFICI 0.05–0.5). Additionally, the pitavastatin-fluconazole combination significantly reduced the biofilm-forming abilities of the tested Candida species by up to 73%, and successfully reduced the fungal burdens in a Caenorhabditis elegans infection model by up to 96%. This study presents pitavastatin as a potent azole chemosensitizing agent that warrant further investigation. [ABSTRACT FROM AUTHOR]

There has been no report about outcome of pitavastatin versus atorvastatin therapy in high-risk patients with hypercholesterolemia. Hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases (n = 664, age = 65, male = 54%, diabetes = 76%, primary prevention = 74%) were randomized to receive pitavastatin 2 mg/day (n = 332) or atorvastatin 10 mg/day (n = 332). Follow-up period was 240 weeks. The primary end point was a composite of cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. The secondary end point was a composite of the primary end point plus clinically indicated coronary revascularization for stable angina. The mean low-density lipoprotein cholesterol (LDL-C) level at baseline was 149 mg/dL. The mean LDL-C levels at 1 year were 95 mg/dL in the pitavastatin group and 94 mg/dL in the atorvastatin group. There were no differences in LDL-C levels between both groups, however, pitavastatin significantly reduced the risk of the primary end point, compared to atorvastatin (pitavastatin = 2.9% and atorvastatin = 8.1%, HR, 0.366; 95% CI 0.170–0.787; P = 0.01 by multivariate Cox regression) as well as the risk of the secondary end point (pitavastatin = 4.5% and atorvastatin = 12.9%, HR = 0.350; 95%CI = 0.189–0.645, P = 0.001). The results for the primary and secondary end points were consistent across several prespecified subgroups. There were no differences in incidence of adverse events between the statins. Pitavastatin therapy compared with atorvastatin more may prevent cardiovascular events in hypercholesterolemic patients with one or more risk factors for atherosclerotic diseases despite similar effects on LDL-C levels. • The study was a first, randomized, prospective trial of two statins therapy. • Pitavastatin reduced more cardiovascular events compared with atorvastatin. • There were no differences in cholesterol profiles between two statin groups. • This may suggest the action of statin beyond cholesterol-lowering effects. • We may reconsider how to use statins for high-risk patients. [ABSTRACT FROM AUTHOR]

A structurally identifiable micro‐rate constant mechanistic model was used to describe the interaction between pitavastatin and eltrombopag, with improved goodness‐of‐fit values through comeasurement of pitavastatin and eltrombopag. Transporter association and dissociation rate constants and passive rates out of the cell were similar between pitavastatin and eltrombopag. Translocation into the cell through transporter‐mediated uptake was six times greater for pitavastatin, leading to pronounced inhibition of pitavastatin uptake by eltrombopag. The passive rate into the cell was 91 times smaller for pitavastatin compared with eltrombopag. A semimechanistic physiologically‐based pharmacokinetic (PBPK) model was developed to evaluate the potential for clinical drug–drug interactions (DDIs). The PBPK model predicted a twofold increase in the pitavastatin peak blood concentration and area under the concentration‐time curve in the presence of eltrombopag in simulated healthy volunteers. The use of structural identifiability supporting experimental design combined with robust micro‐rate constant parameter estimates and a semimechanistic PBPK model gave more informed predictions of transporter‐mediated DDIs. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women worldwide. While doxorubicin is part of the standard therapy for metastatic breast cancer, it has limited success. Pitavastatin has been shown to enhance the anti-cancer activity of certain therapeutics. The current study, therefore, explored the anti-cancer activity of the combined treatment of doxorubicin and pitavastatin in MCF7 breast cancer cells. Cell proliferation and viability assays demonstrated that combined doxorubicin and pitavastatin treatment resulted in synergistic cytotoxicity and cell death. Western blotting analysis showed that pitavastatin treatment resulted in increasing levels of p53 and the cell cycle regulator p21 in both doxorubicin treated and untreated cells. Furthermore, we demonstrated that apoptosis induced by the combined treatment occurs through the intrinsic pathway as evident from the activation of caspase 9, caspase 7 and the reduction of BCL-2 level. This study provides novel evidence to suggest that combined treatment of doxorubicin and pitavastatin may be effectively combined to treat breast cancer with the potential to minimize the side effects associated with high doses of doxorubicin. [ABSTRACT FROM AUTHOR]

This document is a retraction note from the journal Acta Neurochirurgica. The article in question, titled "Preconditioning with pitavastatin, an HMG-CoA reductase inhibitor, attenuates C-Jun N-terminal kinase activation in experimental subarachnoid hemorrhage-induced apoptosis," has been retracted by the Editor-in-Chief due to concerns about the data presented in the figures. The retraction note outlines specific similarities and inconsistencies in the figures and data, and states that the Editor-in-Chief no longer has confidence in the presented data. The authors have not responded to any correspondence from the publisher regarding this retraction. [Extracted from the article]

Repositioning of approved drugs is an alternative time- and cost-saving strategy to classical drug development. Statins are 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors that are usually used as cholesterol-lowering medication, and they also exhibit anti-inflammatory effects. In the present study, we observed that the addition of Pitavastatin at nanomolar concentrations inhibits the proliferation of CD3/CD28 antibody-stimulated human T cells of healthy donors in a dose-dependent fashion. The 50% inhibition of proliferation (IC50) were 3.6 and 48.5 nM for freshly stimulated and pre-activated T cells, respectively. In addition, Pitavastatin suppressed the IL-10 and IL-17 production of stimulated T cells. Mechanistically, we found that treatment of T cells with doses

Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells.

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. The electrode fabrication proceeded with remarkable sensitivity to the determination of PST. The effect of various optimized parameters such as pH, scan rate (ν), accumulation time (tacc), accumulation potential (Uacc) and loading volumes of Ag MP-MWCNT suspension were investigated to evaluate the performance of synthesized electrochemical sensor and to propose a simple, accurate, rapid and economical procedure for the quantification of PST in pharmaceutical formulations and biological fluids. A linear response of PST concentration in the range 2.0×10−7–1.6×10−6 M with low detection (LOD) and quantification (LOQ) limits of 9.66±0.04 nM and 32.25±0.07 nM, respectively, were obtained under these optimized conditions.

Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

To comparison the efficacy and safety of pivastatin calcium and atorvastatin calcium in the Treatment of Coronary Heart Disease. 100 patients with coronary heart disease from March 2016 to December 2018 were divided into the pitavastatin calcium group(n=50) and the atorvastatin calcium group (n=50). The blood glucose(Glu), Glycated hemoglobin(HbA1c), Ultra- sensitive C reaction protein (hsCRP), Total cholesterol (TC), Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol(HDL-C), Acetyltransferase(ALT), Valley grass transaminase(AST), Creatinine(Cr), Creatine kinase (CK)were monitored and compared before treatment and after treatment of 6,12 months. After 6months and 12months treatment the pitavastatin calcium group HDL-C were significantly elevated (P<0.05), hsCRP were significantly lower(P<0.05). After 6months and 12months the atorvastatin calcium group HDL-C and hsCRP compared to before treatment the difference were not statistically(P>0.05). The atorvastatin calcium group HbA1c were elevated after 12months treatment with statistically differences(P<0.05), but the pitavastatin calcium were not elevated(P>0.05). The two groups TC, LDL-C were lower with statistically significant differences(P<0.05). The differences between Glu, ALT, AST, Cr, CK before treatment and after treatment were without statistically differences (P>0.05), 1patient was removed because of transaminase elevated. Both pitavastatin calcium and atorvastatincalcium can lower LDL-C, TC、TG in Coronary Heart Disease patients, Moreover, the pitavastatin calcium can elevate HDL-C level and lower hsCRP level. Meanwhile, the pitavastatin calcium had no evidence in new diabetes, it was efficacy and safety in long-term treatment. [ABSTRACT FROM AUTHOR]

Solidification of a preconcentrate lipid formulation namely self-nano emulsifying drug delivery system (SNEDDS) is required to achieve feasibility, flexibility, and a new concept of "dry nano-emulsion". The purpose of this study was to assess the effect of SNEDDS loading and ethanol as a diluent on the solidification of pitavastatin supersaturable SNEDDS (S-SNEDDS). A 22 full factorial design approach with a center point addition as a curvature was implemented to determine the effect of S-SNEDDS loading and ethanol on the physical characteristics, namely flowability, compactibility, and drug release behavior. Vibrational spectra, thermal behavior, and morphology of solid S-SNEDDS formulation were also evaluated. The results indicated that there was no interaction between S-SNEDDS and carrier, based on vibrational spectra. However, thermal behaviors (enthalpy and weight loss) were depending on SNEDDS loading. Thereafter, the ethanol as a diluent of preconcentrated formulation had no effect on the morphology of carrier structure. However, the S-SNEDDS loading altered the structure of carrier owing to either solubilization or abrasion processes. The statistical model suggested that ethanol as diluent reduced the flowability, compactibility, and drug releases. Meanwhile, the liquid SNEDDS loading affected the reducing of flowability and compactibility. Finally, solidification without diluent and 20% lipid formulation load was recommended. In addition, it was very useful because of ease on handling, flexibility for further formulation, and desired characteristics of final solid dosage form. [ABSTRACT FROM AUTHOR]

To understand the pathways involved in drug clearance from the body, quantitative evaluations of the hepatobiliary transport of drugs are important. The organic anion transporting polypeptide (OATP) family transporter, particularly OATP1B1 and 1B3, are considered to play an important role in hepatic uptake of organic anion compounds. Pitavastatin is a substrate of OATP, and it includes a fluorine group. Therefore, it represents an acceptable positron-emission tomography (PET) tracer using fluorine-18 to image in vivo hepatic transporter functions. [18F]Pitavastatin was synthesized using the method we previously reported. To evaluate the potential of [18F]pitavastatin in PET imaging of in vivo OATP functions, we investigated the hepatic uptake with/without rifampicin as an OATP inhibitor after administration in normal SD rats. [18F]Pitavastatin metabolite was evaluated using reverse-phase thin-layer chromatography (TLC) autoradiography. We subsequently analyzed the PET image results and demonstrated that [18F]pitavastatin selectively accumulated in the liver post-administration. Result and discussion In metabolite analysis using reverse-phase TLC, we found that the radioactivity detected in the plasma, liver (>90% intact), and bile mostly originated from the parent pitavastatin of the PET study (~40 min). [18F]pitavastatin's hepatic uptake decreased (approximately 76%) with rifampicin co-administration in PET analysis. Because [18F]pitavastatin has lower clearance in rats than other previously reported OATP1B PET s, it holds the potential of an imaging tracer that has a higher sensitivity in monitoring hepatic OATP1B function's changes. Compared with the previously reported OATP imaging tracers, [18F]pitavastatin is more suitable for the sensitive detection of functional changes in OATP transporters. We believe that [18F]pitavastatin enables quantitative analysis of the hepatobiliary transport system for organic anion compounds. Unlabelled Image [ABSTRACT FROM AUTHOR]