- |||||||||| Tabrecta (capmatinib) / Incyte, Novartis, Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Suppression of MET signaling mediated by pitavastatin and capmatinib inhibits oral and esophageal cancer cell growth. (Pubmed Central) - Jan 13, 2022
Our findings suggest that GGPS1 expression could be a biomarker in cancer therapy with pitavastatin, and the combination of pitavastatin with capmatinib might be a promising therapeutic strategy in OSCC and ESCC. Implications: This study provides new insight into the mechanism of pitavastatin as an anticancer drug and suggests that the combination of pitavastatin with capmatinib is a useful therapeutic strategy in OSCC and ESCC.
- |||||||||| Xtandi (enzalutamide) / Pfizer, Astellas, Bausch Health, Livalo (pitavastatin) / Kowa, Eli Lilly
Statin type and survival of patients with metastatic castrate-resistant prostate cancer receiving abiraterone and enzalutamide: A nationwide retrospective cohort study. (In-Person & On Demand | Level 1, West Hall) - Jan 5, 2022 - Abstract #ASCOGU2022ASCO_GU_282;
When analyzing statin lipophilicity, we saw a higher trend towards survival in the hydrophilic statin group compared to the lipophilic statin group, which contradicts the direct anticancer benefits of lipophilic statins, but neither group reached statistical significance. Further studies analyzing statin usage and types with specific outcome measures such as cardiovascular events, duration of antiandrogen therapy, and adverse events related to ABI or ENZ will support in optimal therapy choices for mCRPC.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Clinical, Journal: Further Evaluation of Coproporphyrins as Clinical Endogenous Markers for OATP1B. (Pubmed Central) - Dec 23, 2021
In conclusion, CP-I and CP-III in plasma display the potential to be applied as endogenous markers for the evaluation of OATP1B inhibition in clinical trials. While renal transporters contribute significantly to the CL of CP-III, it would be better to investigate the impact of the CL on plasma exposure of CP-III during clinical DDI assessments.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Clinical, Journal: Clinically Administered Doses of Pitavastatin and Rosuvastatin. (Pubmed Central) - Dec 16, 2021
Furthermore, PTV significantly suppressed the angiotensin-II-induced proline incorporation in primary cultured cardiac fibroblasts. In conclusion, a clinical dose of PTV was noted to directly inhibit cardiomyocyte hypertrophy and cardiac fibrosis, suggesting that lipophilic PTV can be a potential drug candidate against chronic heart failure.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: DoE Screening and Optimization of Liquid Chromatographic Determination of Nicotinic Acid and Six Statins: Application to Pharmaceutical Preparations and Counterfeit Detection. (Pubmed Central) - Dec 13, 2021
An isocratic reversed-phase high performance liquid chromatographic method has been developed and validated to simultaneously determine nicotinic acid, pravastatin sodium, rosuvastatin calcium, atorvastatin calcium, pitavastatin calcium, lovastatin sodium and simvastatin sodium in focus on counterfeit drug detection...The developed method was sensitive, accurate, simple, economical and highly robust, in addition to the comprehensiveness and novelty of this method for separating the seven drugs. The results were statistically compared with the reference methods used Student's t-test and variance ratio F-test at P < 0.05.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
DRUG REPURPOSING SCREEN REVEALS GLIOBLASTOMA CELL LINE SUSCEPTIBILITY TO STATINS () - Nov 16, 2021 - Abstract #SNO2021SNO_1220;
BACKGROUND The standard therapy for glioblastoma patients is tumor resection followed by radiotherapy and temozolomide chemotherapy...RESULTS Fluvastatin and pitavastatin produced the most significant effects in glioblastoma cell lines...Here, we found their effects correlated with erastin, an enhancer of ferroptosis and with gene knockout of UBIAD1, which participates in non-mitochondrial ubiquinone synthesis...CONCLUSION Statins appeared to be especially effective against glioblastoma lines and the effect could be linked to ferroptosis and inhibition of UBIAD1. In vitro validation of this finding is ongoing.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Nanoparticle-Mediated Simultaneous Targeting of Mitochondrial Injury and Inflammation Attenuates Myocardial Ischemia-Reperfusion Injury. (Pubmed Central) - Nov 4, 2021
Combined administration of polymeric nanoparticles composed of poly-lactic/glycolic acid and encapsulating nanoparticles containing cyclosporine A or pitavastatin, which inhibit mitochondrial permeability transition pore opening and monocyte-mediated inflammation, respectively, augmented the cardioprotection as compared with single administration of nanoparticles containing cyclosporine A or pitavastatin after myocardial IR injury. Conclusions Nanoparticle-mediated simultaneous targeting of mitochondrial injury and inflammation could be a novel therapeutic strategy for the treatment of myocardial IR injury.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Biomarker, Review, Journal: The Effect of Statin Therapy on Inflammatory Biomarkers: A Systematic Review. (Pubmed Central) - Nov 1, 2021
They were subsequently assessed for risk of bias using a Cochrane risk analysis tool, identifying most as having some concerns of bias or low risk of bias. We found that HMG-CoA reductase inhibitors exhibit both a lipid-lowering effect addition to an anti-inflammatory effect.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Baseline low-density lipoprotein cholesterol predicts the benefit of adding ezetimibe on statin in statin-naïve acute coronary syndrome. (Pubmed Central) - Oct 30, 2021
Kaplan-Meier analyses revealed that the primary endpoint was not significantly different between the treatment groups for the < 131 mg/dL group, however, it was significantly lower in patients treated with pitavastatin + ezetimibe in the ≥ 131 mg/dL group (Hazard ratio = 0.72, 95% confidence interval = 0.56-0.91, P = 0.007, P value for interaction = 0.012). Statin-naïve ACS patients with baseline LDL-C < 131 mg/dL did not clinically benefit from pitavastatin + ezetimibe, while patients with baseline LDL-C ≥ 131 mg/dL treated with pitavastatin + ezetimibe showed better clinical results than those treated with pitavastatin monotherapy.Clinical Trial Registration: Original HIJ PROPER study; URL: http://www.umin.ac.jp/ctr . Unique Identifier; UMIN000002742, registered as an International Standard Randomized Controlled Trial.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Clinical, Journal: Lipid Droplet Accumulation Independently Predicts Poor Clinical Prognosis in High-Grade Serous Ovarian Carcinoma. (Pubmed Central) - Oct 25, 2021
Our cell-based assays thus suggested that enhanced aerobic glycolysis resulted in LD accumulation and activation of survival-related kinases. Overall, our results support the idea that cancers with lipogenic phenotypes are associated with poor clinical prognosis, and we suggest that adipophilin may serve as an independent indicator of a poor prognosis in HGSOC.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Interaction of the pitavastatin with model membranes. (Pubmed Central) - Oct 12, 2021
Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.
- |||||||||| Parmodia (pemafibrate) / Kowa, Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Recent advances in synthetic pharmacotherapies for dyslipidaemias. (Pubmed Central) - Oct 3, 2021
Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the attainment of therapeutic targets.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Statins repress needle-like carbon nanotube- or cholesterol crystal-stimulated IL-1β production by inhibiting the uptake of crystals by macrophages. (Pubmed Central) - Sep 16, 2021
We found that various statins, including pitavastatin, atorvastatin, fluvastatin, and lovastatin, but not squalene synthase inhibitor, repressed IL-1β release upon MWCNT stimulation...The statin-induced repression of MWCNT-elicited IL-1β release was observed in THP-1 derived and mouse peritoneal macrophages, but not in bone marrow-derived macrophages, where statins act in synergy with lipopolysaccharide to enhance the expression of IL-1β precursor protein. In summary, we describe a novel anti-inflammatory mechanism through which statins repress mature IL-1β release induced by pathogenic crystals and nanoneedles by inhibiting the internalization of crystals by macrophages.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Clinical, Journal: Multifunctional silica-coated mixed polymeric micelles for integrin-targeted therapy of pediatric patient-derived glioblastoma. (Pubmed Central) - Sep 11, 2021
Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity...This PTV-loaded nanocarrier triggers apoptosis by reducing the mRNA level of anti-apoptotic genes NF-kβ, IL-6, BIRC1 and BIRC5 by 89%, 33%, 81% and 63%, respectively, and the cell viability by >60%. Overall, our results suggest the potential of these hybrid nanocarriers for the targeted therapy of GBM and other tumors overexpressing integrin receptors.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Observational data, Journal: Candidate drugs for preventive treatment of unruptured intracranial aneurysms: A cross-sectional study. (Pubmed Central) - Sep 9, 2021
Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i-CPFs loaded with PITA as osteogenic and angiogenic agent. The present analysis suggests that several types of statins, calcium channel blockers, and ARBs are candidate drugs for preventive treatment of unruptured IAs.
- |||||||||| pitavastatin / Generic mfg.
Trial completion, Trial completion date, Trial primary completion date: K-924 Phase III Long Term Study (clinicaltrials.gov) - Sep 5, 2021
P3, N=110, Completed,
Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression. Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> Aug 2021 | Trial primary completion date: Dec 2021 --> Aug 2021
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation. (Pubmed Central) - Aug 29, 2021
Mevalonic acid, cholesterol and the MEK1/2 inhibitor U0126 reversed this Pitavastatin-mediated ERK1/2 activation and apoptosis of T cells. In summary, our results suggest that Pitavastatin is a highly potent inhibitor of T-cell proliferation, which induces apoptosis via pro-apoptotic ERK1/2 activation, thus representing a potential repositioning candidate for the treatment of T-cell-mediated autoimmune diseases.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Application of a Reactive Oxygen Species-Responsive Drug-Eluting Coating for Surface Modification of Vascular Stents. (Pubmed Central) - Aug 27, 2021
In addition, the coating was used as a drug carrier to load pitavastatin calcium...A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Comparing different types of statins for secondary prevention of cardio-cerebrovascular disease from a national cohort study. (Pubmed Central) - Aug 25, 2021
After adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456-2.005), 1.347 (0.354-5.116), and 0.943 (0.317-2.803), respectively, when compared with the simvastatin group. There were no significant differences between the statins in efficacy for preventing recurrence of CCVD events and/or death in CCVD patients.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Pre-incubation with OATP1B1 and OATP1B3 inhibitors potentiates inhibitory effects in physiologically relevant sandwich-cultured primary human hepatocytes. (Pubmed Central) - Aug 14, 2021
The current study was designed to determine the IC values of OATP1B1 and OATP1B3 inhibitors everolimus (EVR), sirolimus (SIR), and dasatinib against OATP1B substrates in physiologically relevant primary human hepatocytes with or without inhibitor-preincubation and to compare the OATP-mediated DDI prediction using data from primary human hepatocytes and that reported previously in transporter-expressing cell lines...Accumulation of [H]-CCK-8 (1 µM, 1.5 min), [H]-rosuvastatin (0.5 µM, 2 min) and [H]-pitavastatin (1 µM, 0.5 min) was determined in human sandwich-cultured hepatocytes (SCH) in the presence of vehicle control or an inhibitor with or without inhibitor-preincubation at designated concentrations, and was utilized to determine the IC values for these inhibitors...In conclusion, the current study is the first to report that pre-incubation with OATP1B inhibitors potentiates inhibitory effects in physiologically relevant primary human hepatocytes, supporting the rationale of the current US FDA draft guidance of including an inhibitor-preincubation step when assessing OATP-mediated DDIs in vitro. IC values after inhibitor-preincubation in transporter-expressing cell lines may be used for DDI prediction for the purpose of mitigating false-negative OATP-mediated DDI prediction.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: LDL subclass lipidomics in atherogenic dyslipidemia:Effect of statin therapy on bioactive lipids and dense LDL. (Pubmed Central) - Aug 8, 2021
Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study...Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: In silico interactions of statins with cell death-inducing DNA fragmentation factor-like effector A (CIDEA). (Pubmed Central) - Aug 4, 2021
The docking results indicated that atorvastatin and rosuvastatin showed the best interaction energy (-8.51 and -8.04 kcal/mol, respectively) followed by fluvastatin (-7.39), pitavastatin (-6.5), lovastatin (-6.23), pravastatin (-6.04) and simvastatin (-5.29)...Since two arginine residues -ARG19 and ARG22-were identified to be common for the interaction with CIDEA, a single-point mutation was induced in these residues to determine whether they are important for binding interaction. Mutation of these two residues seems to affect mostly the interaction of atorvastatin with CIDEA, suggesting that they are important for the binding and therefore indicate another possible metabolic mechanism of the pleiotropic effects of this statin.
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