Pitavastatine

Pitavastatin, a potent 3-hydroxymethylglutaryl coenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and mixed dyslipidemia. Hepatic uptake of pitavastatin is predominantly occupied by the organic anion transporting polypeptide 1B1 (OATP1B1) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene, which is a polymorphic gene that encodes OATP1B1. SLCO1B1 genetic polymorphism significantly alters the pharmacokinetics of pitavastatin. This study aimed to establish the physiologically based pharmacokinetic (PBPK) model to predict pitavastatin pharmacokinetics according to SLCO1B1 genetic polymorphism...

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The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) study found a 35% reduction in major adverse cardiovascular events for people with human immunodeficiency virus who received daily pitavastatin. However, how this evidence will change practice is far from certain. Here, we outline evidence gaps and political and healthcare delivery challenges that will need to be addressed for REPRIEVE to offer public health benefits in low- and middle-income countries.

ConspectusFinding efficient synthetic methods for the asymmetric synthesis of complex molecules has always been of interest to organic chemists. Creating and controlling the stereochemistry of stereogenic centers bearing branched allylic moieties in organic molecules using a catalytic process is an attractive and successful method for the synthesis of several natural products and medicinally important compounds. Remarkable progress toward their synthesis has been achieved via transition-metal catalysis, especially in the case of allylic substitution and allylic C-H oxidation chemistry...

Pitavastatin (PITA) is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti-cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5-200 μM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h...

BACKGROUND: Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in cholesterol synthesis. While a rare disorder, malignant transformation to squamous cell carcinoma is seen in up to 11% of cases. Recently, topical cholesterol and topical statin therapy have been suggested as a pathogenesis-directed treatment for porokeratosis. METHODS: A PubMed/MEDLINE and Embase literature search was performed using the search terms: "porokeratosis" AND "cholesterol" OR "lovastatin" OR "simvastatin" OR "atorvastatin" OR "fluvastatin" OR "pitavastatin" OR "pravastatin" OR "rosuvastatin" OR "statin...

Fighting breast tumors mandates finding different agents devoid of chemotherapy side effects. Repurposing existing drugs, such as statins, presents a promising avenue for the development of novel cancer therapeutics. Based on the different effects of statin members, this study aims to evaluate the effect of two of the most promising lipophilic statins, Simvastatin and Pitavastatin, and their combination with a conventional chemotherapeutic regimen of doxorubicin and cyclophosphamide on breast cancer cells. MDA-MB-231 and MCF7 cell lines were used to analyze the effects of Pitavastatin and simvastatin in combination with doxorubicin/cyclophosphamide...

Canine oral melanoma is a highly malignant cancer with a poor prognosis. Statins, commonly used drugs for treating dyslipidemia, exhibit pleiotropic anticancer effects and marked anti-proliferative effects against melanoma cells. The anticancer effects among statins vary; in human cancers, lipophilic statins have shown stronger anticancer effects compared with hydrophilic statins. However, data on the differences in the effects of various statins on canine cancer cells are lacking, hence the optimal statins for treating canine melanoma remain unknown...

Tissue drug concentrations determine the efficacy and toxicity of drugs. When a drug is the substrate of transporters that are present at the blood:tissue barrier, the steady-state unbound tissue drug concentrations cannot be predicted from their corresponding plasma concentrations. To accurately predict transporter-modulated tissue drug concentrations, all clearances (CLs) mediating the drug's entry and exit (including metabolism) from the tissue must be accurately predicted. Since primary cells of most tissues are not available, we have proposed an alternative approach to predict such CLs, that is the use of transporter-expressing cells/vesicles (TECs/TEVs) and relative expression factor (REF)...

BACKGROUND: Emergency percutaneous coronary intervention (PCI) can quickly restore myocardial perfusion after acute coronary syndrome. Whether and which lipid-lowering regimens are effective in reducing major adverse cardiovascular events (MACEs) and mortality risk after PCI remain unclear. OBJECTIVE: This study assessed the benefits of different lipid-lowering regimens on the risk of MACEs and mortality in the post-PCI population by network meta-analysis. METHODS: Public databases, including PubMed, Embase and the Cochrane Library, were searched from inception to August 2022...

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022...

PURPOSE: To investigate the impact of statin use on primary prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in a dose-, class-, and use intensity-dependent manner. METHODS: We used an inverse probability treatment-weighted Cox hazards model, with statin use status as a time-dependent variable. RESULTS: Our results showed that statin use was associated with a significant reduction in CVD risk with an adjusted hazard ratio of 0...

Combination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γc ). PD-1 ligation also activates SHP2, which dephosphorylates γc Y357 , leading to impairment of γc family cytokine-triggered signaling...

Grinspoon SK, Fitch KV, Zanni MV, et al; REPRIEVE Investigators. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389:687-699. 37486775.

Background and Objectives : We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits' intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods : Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N...

AIM: This article summarizes key research presented at the International AIDS Society (IAS) Conference in Brisbane, held in July 2023. CO-MORBIDITIES: The REPRIEVE Trial as a conference highlight, demonstrating significantly fewer major cardiovascular events amongst people with HIV who were randomized to pitavastatin compared to placebo. Key data on weight, hypertension and incident diabetes are also summarized. ANTIRETROVIRAL THERAPY: Novel data on doravirine and islatravir are described as are trials demonstrating efficacy dolutegravir/lamivudine first-line in people without baseline resistance testing and in suppressed switch amongst people with historic lamivudine resistance...

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death. METHODS: Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate...

Background: The pathogenic genes of colorectal cancer (CRC) have not yet been fully elucidated, and there is currently a lack of effective therapeutic targets. This study used bioinformatics methods to explore and experimentally validate the most valuable biomarkers for colorectal cancer and further investigate their potential as targets. Methods: We analyzed differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset and screened out hub genes. ROC curve and univariate Cox analysis of The Cancer Genome Atlas (TCGA) dataset revealed the most diagnostically and prognostically valuable genes...

Hepatic impairment (HI) moderately (< 5-fold) affects the systemic exposure (i.e. area under the plasma concentration-time curve, AUC) of drugs that are substrates of the hepatic sinusoidal organic anion transporting polypeptide (OATP) transporters and are excreted unchanged in the bile and/or urine. However, the effect of HI on their AUC is much greater (> 10-fold) for drugs that are also substrates of cytochrome P450 (CYP) 3A enzymes. Using the extended clearance model, through simulations, we identified the ratio of sinusoidal efflux clearance (CL) and the sum of metabolic and biliary CLs as important in predicting the impact of HI on the AUC of dual OATP/CYP3A substrates...

A sol-gel Carbowax 20 M/3-[(3-Cholamidopropyl) dimethyl ammonio]-1-propanesulfonate composite sorbent-based capsule phase microextraction device has been fabricated and characterized for the determination of four statins (pravastatin, rosuvastatin, pitavastatin, and atorvastatin) in human urine. The presence of ionizable carboxyl functional groups in statins requires pH adjustment of the sample matrix to ensure that the target molecules are in their protonated form (pH should be 2 units below their pKa values) which not only is cumbersome but also risks unintended contamination of the sample...