Effects of Zhibitai capsule combined with pitavastatin calcium tablets on coronary heart disease complicated with diabetes mellitus / 中国基层医药

Objective:To investigate the effects of Zhibitai capsule combined with pitavastatin calcium tablets on blood lipids, blood glucose, and glycated hemoglobin in patients with coronary heart disease complicated by diabetes mellitus. Methods:A total of 100 patients with coronary heart disease and diabetes mellitus who received treatment in The Third Affiliated Hospital of Jinzhou Medical University from January 2017 to June 2020 were included in this study. They were divided into a control group ( n = 50) and an observation group ( n = 50) according to different treatment methods. Both groups were given conventional treatment such as pitavastatin calcium tablets. The control group was given pitavastatin calcium tablets based on conventional treatment. The observation group was given Zhibitai capsule combined with pitavastatin calcium tablets based on conventional treatment. After 6 months of treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and glycated hemoglobin were compared between the two groups. Results:After treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, glycated hemoglobin in the observation group were (4.26 ± 0.67) mmol/L, (1.85 ± 0.38) mmol/L, (3.16 ± 0.27) mmol/L, (8.29 ± 1.07) mmol/L, and (8.20 ± 0.77)%, respectively, and they were (4.50 ± 0.39) mmol/L, (1.99 ± 0.19) mmol/L, (3.28 ± 0.27) mmol/L, (8.80 ± 0.66) mmol/L, (8.54 ± 0.74)%, respectively in the control group. After treatment, these indices in each group were decreased compared with those before treatment (control group: t = 19.56, 14.60, 10.66, 8.60, 10.18; observation group: t = 15.04, 14.68, 11.36, 12.36, 12.89, all P < 0.05). After treatment, these indices in the observation group were significantly lower than those in the control group ( t = -2.12, -2.23, 2.26, -2.84, -2.44, all P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation and control groups was (1.16 ± 0.18) mmol/L and (1.09 ± 0.13) mmol/L, respectively. After treatment, the level of high-density lipoprotein cholesterol in each group was increased compared with that before treatment (control group: t = -11.10, observation group: t = -11.07, P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation group was significantly higher than that in the control group ( t = 2.11, P < 0.05). Conclusion:Zhibitai capsule combined with pitavastatin calcium tablets can greatly improve the level of blood lipids and blood glucose in patients with coronary heart disease complicated by diabetes mellitus.

Validated Kinetic Spectrophotometric Determination Of Pitavastatin Calcium Using Acidic Permanganate Oxidation

Objective: Development and validation of a sensitive, indirect spectrophotometric kinetic method, based on oxidation-reduction reaction, using potassium permanganate, for the quantitative assay of pitavastatin calcium, a cardiovascular drug used for the treatment of hyperlipidemia. Methods: The developed spectrophotometric kinetic method is based on the ability of potassium permanganate to oxidize Pitavastatin, where, the drug solution is treated with a fixed concentration of permanganate in acidic medium, and after a specified time, the unreacted permanganate is measured at 525 nm. All variables affecting the color development have been investigated and the conditions were optimized. Different kinetic methods, including initial rate, rate constant, fixed time and fixed concentration, were applied for the determination Pitavastatin. Results: During the course of the reaction, the absorbance values, at 525 nm, related to KMnO4, decreased linearly with increasing the concentration of the drug. The reaction rate obeyed was found to be pseudo-first-order and the kinetic method used was the fixed-time method. The assay of PITA in the concentration range of 16-80 μg/ml, using the fixed time method was successfully determined with a correlation coefficient value of 0.9999. The applicability of the developed method was also demonstrated by the determination of pitavastatin in its pure form and in its pharmaceutical formulation, where, the effect of excipients has also been studied and found to have no effect. Conclusion: The developed indirect spectrophotometric kinetic method, using the fixed time method, was used for the determination of Pitavastatin in pharmaceutical tablets. This method was simple, accurate and easy to apply for routine assay and in quality control laboratories.

Effect of Pitavastatin in Patients with Active Rheumatoid Arthritis Treated at a Tertiary Care Hospital

Introduction: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder, autoimmune in nature that predominatelyaffects synovial joints. Being a crippling disease is a leading cause of disability that often reduces the quality of life and impairspatients ability to work.Aims and Objectives: The aim of the study was to compare the effect of different treatment regimens on patients with activeRA treated at a tertiary care hospital.Materials and Methods: This was a prospective, open labeled, parallel arm, randomized, and single-center study performed ina tertiary care teaching hospital (Chennai Medical College Hospital and Research Centre [SRM Groups], Irungalur, Tiruchirapalli)and was conducted at outpatient clinics. Total duration of the study period was 24 weeks. All the patients were having activeRA and were on oral methotrexate (first-line disease-modifying antirheumatic drug) at the time of recruitment.Statistical Analysis: All the data were initially entered into Microsoft Excel 2010 and later these spreadsheets were used foranalysis. Statistical analysis was done using SPSS version 20.0.Conclusion: Combination therapy of pitavastatin and methotrexate is better than methotrexate monotherapy and combinationtherapy of rosuvastatin and methotrexate.

Development and validation of RP-HPLC method for pitavastatin calcium in bulk and formulation using experimental design

The optimization of HPLC method involves several variables whose influence has been widely studied. However, inmost of the cases, only process variables are taken into account. In this work, the influence of mixture compositionon peak quality parameters of Pitavastatin calcium in bulk and tablet dosage form has been studied using a mixturesimplex design. A simplex centroid design with axial points in a pseudo-component representation was generated fromthe pure mixture components. Twelve ternary mixture mobile phases corresponding to augmented design points weretested to separate the drug in sample. The statistical analysis was performed to generate the polynomial equation foreach response. The desirability approach was used to determine the optimal mobile phase composition. Furthermore,the method was validated as per the ICH guidelines using specificity, linearity, accuracy, precision, sensitivity, systemsuitability, and robustness. The results of experimental design were statistically tested for full and in portion to getbest fitted model which accurately describe changes in the proportion of these solvents in the mobile phase close to theregion of optimal peak quality. The method demonstrated optimum chromatographic separation with isocratic elutionof the mobile phase containing a mixture of acetonitrile-water (pH 3.0)-tetrahydrofuran (43:55:02, v/v/v) with a flowrate at 1.0 ml/minute. Design of experiment optimization strategy is a powerful tool to acquire the maximum qualitydata while performing minimum number of experiments. The mobile phase composition was successfully optimizedusing simplex centroid mixture design with desirability approach. Additionally, developed method can be appliedfor routine quantitative analysis of Pitavastatin calcium in bulk and tablet dosage form as it was found to be simple,sensitive, and robust.

Influence of pitavastatin on insulin resistance in CHD + NAFLD patients with normal liver function and its safety analysis／ / 心血管康复医学杂志

To explore influence of pitavastatin on insulin resistance (IR ) in patients with coronary heart disease (CHD) complicated non‐alcoholic fatty liver disease (NAFLD ) and normal liver function and its safety . Methods :A total of 205 CHD + NAFLD patients from our hospital were selected as NAFLD group ,another 70 CHD patients without NAFLD were regarded as non‐NAFLD group .According to NAFLD severity ,NAFLD group was further divided into NAFLD mild group (n＝87) ,moderate group (n＝64) and severe group (n＝54).All pa‐tients received pitavastatin based on routine treatment for 12 weeks .Homeostasis model‐insulin resistance index (HOMA‐IR) before and after treatment ,and incidence rate of severe liver damage were observed and compared a‐mong four groups .Results :Compared with before treatment ,there was significant reduction in HOMA‐IR in four groups after treatment , P＝0. 001 all.Compared with non‐NAFLD group before treatment ,there was significant rise in HOMA‐IR [(3.08 ± 0. 35) vs.(3. 65 ± 0.42) vs.(4. 12 ± 0. 31) ,(4.21 ± 0.47)] in mild ,moderate and severe group ,and those of moderate and severe group were significantly higher than that of mild group , P＝0. 001 all ;af‐ter treatment ,compared with non‐NAFLD group , the HOMA‐IR of mild group was no significant difference ,but compared with non‐NAFLD group and mild group there was significant rise in HOMA‐IR [ (2. 54 ± 0.38) ,(2. 61 ± 0.47) vs.(2.97 ± 0. 35 ) ,(3. 08 ± 0.44)] in moderate and severe group , P＝ 0.001 all.There was no significant difference in incidence rate of severe liver damage among four groups , P＝0. 872. Conclusion :Pitavastatin can sig‐nificantly reduce HOMA‐IR with good safety in CHD + NAFLD patients with normal liver function ,which is worth extending .

Meta-analysis of Pitavastatin Comparison of Atorvastatin in the Treatment of Primary Hyperlipidemia in Chinese Adults / 中国药房

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of pitavastatin comparison of atorvastatin in the treatment of primary hypedipemia in Chinese adults,and to provide evidence-based reference for clinic.METHODS:Retrieved from The Cochrane Library,PubMed,Chinese Journal Full-text Database,Wanfang database,and manually search Google Scholar,Baidu academic search engine,randomized controlled trials (RCTs) about pitavastatin (trial group) vs.atorvastatin (control group) in the treatment of primary hyperlipemia in Chinese adults were collected.After literature screening,data extraction,quality evaluation of included studies with modified Jadad scale,Meta-analysis of the levels of total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C),response rate and the incidence of ADR was conducted by using Rev Man 5.3 statistical software.RESULTS:A total of 5 RCTs were included,involving 456 patients.Results of Meta-analysis showed that the decrease of TC level [MD=0.09,95％CI(0.01,0.16),P=0.03] in trial group was more better than control group,while the increase of HDL-C level [MD=0.08,95％ CI (0.01,0.14),P=0.03] and the decrease of the TG level [MD=-0.13,95％ CI (-0.20,-0.06),P=0.000 4] in trial group were worse than control group,with statistical significance.There was no statistical difference in the decrease of LDL-C[MD=-0.01,95％ CI (-0.13,0.10),P=0.84],response rate [OR=0.75,95％CI (0.15,3.66),P=0.72] or the incidence of ADR [OR=0.68,95 ％ CI (0.44,1.05),P=0.08] between 2 groups.CONCLUSIONS:Pitavastatin has better therapeutic efficacy in decreasing TC,but its therapeutic efficacy in decreasing LDL-C is similar to that of atorvastatin;its therapeutic efficacy in decreasing TG and increasing HDL-C is worse than that of atorvastatin.The safety of them is equivalent.

Influence of pitavastatin on vascular endothelial function in young and middle-aged patients with hyperlipidemia complicated carotid plaques / 心血管康复医学杂志

Objective: To explore therapeutic effect of pitavastatin on young and middle-aged patients with hyperlipidemia complicated carotid plaques and its influence on vascular endothelial function. Methods: A total of 126 young and middle-aged patients with hyperlipidemia complicated carotid plaques [carotid intima-media thickness (IMT) ＞ 1. 5mm]were selected, and were randomly divided into no lipid lowering treatment group (n=62) and pitavastatin group (n=64). Flow-mediated dilation of brachial artery (FMD), carotid IMT and blood lipid levels before and 12 months after medication, and incidence rate of adverse events were recorded and compared between two groups. Results: Compare with before treatment and no lipid lowering treatment group after treatment, there was significant rise in FMD [(6. 70±2. 10) ％, (6. 60±2. 35) ％ vs. (8. 90±3. 60) ％], and significant reductions in levels of total cholesterol [(6. 05±1. 40) mmol/L, (5. 67±1. 90) mmol/L vs. (4. 05±1. 20) mmol/L], triglyceride [(2. 18± 0. 72) mmol/L, (2. 08±0. 68) mmol/L vs. (1. 77±0. 65) mmol/L]and low density lipoprotein cholesterol [(4. 65±1. 50) mmol/L, (4. 41±1. 36) mmol/L vs. (2. 01±1. 30) mmol/L]in pitavastatin group, P＜0. 05 or＜0. 01; there were no significant changes in IMT in two groups. No obvious adverse reaction was found in pitavastatin group. Conclusion: Pitavastatin can significantly improve lipid levels and vascular endothelial function in young and middle-aged patients with hyperlipidemia complicated carotid plaques.

Electrochemical determination of an anti-hyperlipidimic drug pitavastatin at electrochemical sensor based on electrochemically pre-treated polymer film modified GCE / 药物分析学报

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.

Preparation of pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles and their effects on proliferation of endothelial progenitor cells / 中国药科大学学报

@#The objectives of this study were to prepare pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles(PLGA), to characterize their pharmaceutical properties, to conduct in vitro drug-release from the nanoparticles, and to observe the effects on the proliferation of endothelial progenitor cells. Both pitavastatin-loaded PLGA and blank PLGA nanoparticles were prepared using emulsion-solvent diffusion method with PLGA being carrier materials. Morphology of the nanoparticles was observed by scanning electron microscopy(SEM), and particle size was analyzed by laser nanometer particle size analyzer. The drug loading and encapsulation efficiency were assayed using high-performance liquid phase. Impact of blank and pitavastatin-loaded nanoparticles on the viability of endothelial progenitor cells was investigated by CCK8 method. Pitavastatin-loaded PLGA nanoparticles exhibited the structure with spherical shape, smooth surface and average diameter of(230. 1±45)nm. The drug loading capacity and encapsulation efficiency were(10. 00±1. 83)% and(35. 54±5. 40)%, respectively. In vitro sustained-release of pitavastatin from the nanoparticles was found. The blank PLGA nanoparticles had no effect on the viability of the endothelial progenitor cells in different concentrations. Compared with pitavastatin group, pitavastatin-loaded nanoparticles(0. 01 μmol/L, 0. 1 μmol/L)had more effects on the proliferation of endothelial progenitor cells. In conclusion, emulsion-solvent diffusion method is applicable in preparation of pitavastatin-loaded PLGA nanoparticles with good shape and sustained-release of interest. Pitavastatin-loaded nanoparticles could significantly improve proliferation of the endothelial progenitor cells.

Effect of Pitavastatin Treatment on ApoB-48 and Lp-PLA2 in Patients with Metabolic Syndrome: Substudy of PROspective Comparative Clinical Study Evaluating the Efficacy and Safety of PITavastatin in Patients with Metabolic Syndrome

BACKGROUND: Apolipoprotein (Apo) B-48 is an intestinally derived lipoprotein that is expected to be a marker for cardiovascular disease (CVD). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vascular-specific inflammatory marker and important risk predictor of CVD. The aim of this study was to explore the effect of pitavastatin treatment and life style modification (LSM) on ApoB-48 and Lp-PLA2 levels in metabolic syndrome (MS) patients at relatively low risk for CVD, as a sub-analysis of a previous multi-center prospective study. METHODS: We enrolled 75 patients with MS from the PROPIT study and randomized them into two treatment groups: 2 mg pitavastatin daily+intensive LSM or intensive LSM only. We measured the change of lipid profiles, ApoB-48 and Lp-PLA2 for 48 weeks. RESULTS: Total cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and ApoB-100/A1 ratio were significantly improved in the pitavastatin+LSM group compared to the LSM only group (P≤0.001). Pitavastatin+LSM did not change the level of ApoB-48 in subjects overall, but the level of ApoB-48 was significantly lower in the higher mean baseline value group of ApoB-48. The change in Lp-PLA2 was not significant after intervention in either group after treatment with pitavastatin for 1 year. CONCLUSION: Pitavastatin treatment and LSM significantly improved lipid profiles, ApoB-100/A1 ratio, and reduced ApoB-48 levels in the higher mean baseline value group of ApoB-48, but did not significantly alter the Lp-PLA2 levels.

A comparative study of efficacy and safety of pitavastatin versus atorvastatin in the patients of dyslipidemia in medicine department of a tertiary care teaching hospital.

Background: Cardiovascular diseases (CVDs) are the major cause of death globally. Dyslipidemia is one of the most significant risk factors for CVD. 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitors (statins), which are used for the treatment of dyslipidemia, has a beneficial effect in both primary and secondary prevention of CVD. Hence, this study was done to compare the efficacy and safety of atorvastatin versus pitavastatin in patients of dyslipidemias. Methods: After obtaining ethical clearance from institution and written informed consent from patients, 100 patients included in the study were randomly allocated to any of the following two groups. (1) Group A: Tablet atorvastatin 10 mg given orally once a day for 12 weeks. (2) Group B: Tablet pitavastatin 2 mg given orally once a day for 12 weeks. The primary endpoint of the study was a comparative assessment of change in lipid profile (triglyceride, low-density lipoprotein [LDL], high-density lipoprotein [HDL]) from baseline and after 12 weeks. The secondary endpoint involved recording all the adverse effects during the study. Results: Analysis of the baseline and post 12 weeks lipid levels by non-parametric unpaired t-test showed a statistically significant increase in HDL-cholesterol (HDL-C) in Group B as compared to Group A (p=0.028 i.e. p<0.05). However, there was no significant difference between two groups in decreasing LDL-cholesterol (LDL-C) (p=0.615). Conclusions: In this study, pitavastatin is found to be more efficacious than atorvastatin in increasing HDL-C levels, while as efficacious as atorvastatin in decreasing LDL-C in dyslipidemic patients. Atorvastatin is better tolerated than pitavastatin.

Comparison of the hyperlipidemic models and lipid-lowering pharmacodynamics between Dunkin Hartley albino guinea pigs and Hartley pigment guinea pigs / 中国比较医学杂志

ObjectiveTocomparethedifferencesoftwostocksofguineapigs,thealbinoguineapigsandpigment guinea pigs , in establishing dyslipidemic model , to evaluate their lipid-lowering action , and to compare their properties for development of hyperlipidemia .Methods Two stocks of the 5-week-old guinea pigs were randomly divided into two groups, normal group (NC) and model group (Model).For the NC group, 12 guinea pigs were fed with normal chew .For the model group , after fed with high-fat diet for four weeks , 24 male guinea pigs were randomly grouped and treated with vehicle (VC group) and pitavastatin (Pit group) calcium, respectively, by gavage as well as received high-fat diet.Before and after modeling and pitavastatin treatment , blood samples were collected and subjected to analysis of plasma TC , TG, HDL-C and LDL-C, respectively .Results In the normal group , the blood lipid levels of albino guinea pigs were more stable than that of the pigmented pigs with the increase of age .After fed with high-fat diet , the plasma lipid levels of TC , TG and LDL-C were significantly increased in the two strains of guinea pigs , while HDL-C showed a decrease to varying degrees .Interestingly , the lipid level in the albino guinea pigs was significantly higher than that of pigment guinea pigs . And also, after drug administration for four weeks , pitavastatin treatment significantly decreased the elevated lipid level of TC, TG and LDL-C in the albino guinea pigs compared with that in the pigment guinea pigs .Conclusions The albino guinea pigs and pigment guinea pigs demonstrate certain differences in establishing dyslipidemic model and evaluating lipid -lowering pharmacodynamics .However , compared with the pigment guinea pigs , the albino guinea pigs have obvious superiority because of easy establishment of hyperlipidemia model and are more sensitive to lipid -lowering drugs .

The effects of pitavastatin on the related inflammatory factors in patients with early-stage diabetic nephropathy / 中国医师进修杂志

Objective To investigate the protective effect of pitavastatin on the patients with earlystage diabetic nephropathy and its mechanism.Methods Seventy cases of early-stage type 2 diabetic nephropathy were divided into pitavastatin group and regular treatment group by random digits table method with 35 cases each.Meanwhile,35 healthy adults with physical examination were recruited as control group.Before and after treatment in pitavastatin group and regular treatment group and on the day of physical examination in control group,the blood glucose,blood lipid,renal function,urinary albumin excretion rate (UAER),high-sensitivity C-reactive protein (hs-CRP),tumor necrosis factor (TNF)-α,interleukin (IL)-18 were determined and compared.Results Before treatment,the levels of total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),triglycerides (TG),fasting blood sugar,2 h postprandial blood glucose,glycosylated hemoglobin,UAER,hs-CRP,TNF-α,IL-18,HDL-C were (5.74 ± 1.35) mmol/L,(3.73 ± 0.75) mmol/L,(3.46 ± 1.87) mmol/L,(10.25 ± 2.36) mmol/L,(15.59 ± 3.64) mmol/L,(8.67 ± 2.28)％,(124.2 ± 52.5) μg/min,(3.64 ± 1.48) mg/L,(43.74 ± 8.35) μ g/L,(113.43 ± 32.75) ng/L,(1.15 ± 0.36) mmol/L in regular treatment group and (5.93 ± 1.41) mmol/L,(3.68 ± 0.71) mmol/L,(3.29 ± 1.92) mmol/L,(10.48 ± 2.69) mmol/L,(16.04 ± 3.16) mmol/L,(9.48 ± 2.46)％,(116.2 ± 50.4) μ g/min,(3.48 ± 1.46) mg/L,(45.93 ± 9.41) μg/L,(120.68 ±35.20) ng/L,(1.18 ±0.35) mmol/L in pitavastatin group,and (4.57 ±0.83) mmol/L,(2.87 ± 0.64) mmol/L,(1.37 ± 0.58) mmol/L,(4.57 ± 1.37) mmol/L,(7.38 ± 1.30) mmol/L,(5.84 ± 1.57)％,(14.8 ± 9.4) μ g/min,(0.84 ± 0.52) mg/L,(10.42 ± 2.83) μ g/L,(20.84 ± 8.56) ng/L,(1.54 ± 0.39) mmol/L in control group.Before treatment,the levels of TC,LDL-C,TG,fasting blood sugar,2 h postprandial blood glucose,glycosylated hemoglobin,UAER,hs-CRP,TNF-α,IL-18 in regular treatment group and pitavastatin group were higher than those in control group,HDL-C was lower than that in control group,and there were significant differences(P ＜ 0.01).The levels of TC,LDL-C,TG were (4.42 ± 1.28),(3.20 ± 0.57),(2.02 ± 0.87) mmol/L after treatment in pitavastatin group,which were lower than those before treatment,and there were significant differences (P ＜ 0.01).The levels of UAER,hs-CRP,TNF-α,IL-18 were (88.3 ± 36.7) μ g/min,(2.54 ± 0.76) mg/L,(35.62 ± 5.28) μg/L,(83.23 ± 21.57) ng/L in regular treatment group and (64.8 ± 34.6)μ g/min,(2.19 ± 0.65) mg/L,(27.70 ± 7.58) μ g/L,(63.20 ± 18.67) ng/L in pitavastatin group after treatment,which were lower than those before treatment,but the decreased degree was obvious in pitavastatin group.Conclusions Pitavastatin can significantly reduce not only UAER,but also the levels of hs-CRP,TNF-α,IL-18,while effectively lower the blood lipid,in early diabetic nephropathy,which indicates that pitavastatin can reduce urine protein and protect renal function by inhibiting the inflammatory process.

Effects and Mechanism of Pitavastatin on Monocrotaline-induced Pulmonary Arterial Hypertension in Rats / 医药导报

Objective To investigate the effects and mechanism of pitavastatin on monocrotaline ( MTC )-induced pulmonary arterial hypertension ( PAH) in rats. Methods A total of 50 male Sprague-Dawley rats were randomly divided into five groups (n=10 each):pitavastatin treatment at low dose (1 mg·kg-1·d-1),treatment at high dose (3 mg·kg-1·d-1), pitavastatin prevention regimen (1 mg·kg-1·d-1), model control group, and the normol control group. PAH was induced by applying a single subcutaneous injection of MTC(55 mg·kg-1)in the first four groups of rats. The treatment lasted for 8 weeks. At the end of the study, survival rates and mean pulmonary arterial pressure ( mPAP ) among groups were compared. The expression levels of platelet-derived growth factor-B ( PDGF-B) and IL-6, Rac1 mRNA in small pulmonary artery were also detected. Results All rats in the prevention protocol and normal control group survived. Pitavastatin treatment improved survival in the treatment protocol(P<0. 01). The survival rate in the low dose, high dose, and model control group was 60. 0%, 80. 0%, and 40. 0%, respectively. Pitavastatin in both prevention or treatment protocol significantly lowered mPAP (P<0. 01). Pitavastatin also inhibited PDGF-B and IL-6 expression (P<0. 01),and inhibited Rac1 mRNA expression in lung tissues (P<0. 01). Conclusion Pitavastatin reduces mPAP in the MTC-induced PAH rat model, the mechanism of which may be related to inhibition of Rac1 expression,smooth muscle cell proliferation and inflammatory mediator IL-6.

Pitavastatin Regulates Ang II Induced Proliferation and Migration via IGFBP-5 in VSMC

Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II-stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension.

Effects of intensive versus mild lipid lowering by statins in patients with ischemic congestive heart failure: Korean Pitavastatin Heart Failure (SAPHIRE) study

BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.

The effect of pitavastatin on blood glucose and its efficacy in diabetic patients with hypercholesterolemia / 中华内科杂志

Objective To evaluate the effect of pitavastatin on blood glucose in patients with hypercholesterolemia,and to investigate the efficacy of pitavastatin in diabetic patients combined with hypercholesterolemia.Method This study was a 12-week,multi-center,open-label,without parallel-group comparison,phase Ⅳ clinical trail.Results Contrasting to baseline,the prevalences at week 4 and 12 post-treatment of abnormal fasting plasma glucose (FPG) and glycosylated hemoglobin Alc (HbA1c)( FPG:14.2％ vs 14.1％ and 11.0％ ; HbA1c:14.3％ vs 15.1％ and 16.1％ ) in the safety set subjects without diabetes mellitus (DM),as well as in those with DM but not taking glucose-lowering drugs (FPG:7/7 vs 4/7 and 5/7; HbAlc:5/5 vs 4/4 and 5/5) had no significant changes (all P vaules ＞0.05).Contrasting to baseline,the levels of TC [ (6.51±0.94) mmol/L vs (5.12 ±0.93) mmol/L and (4.54 ±1.00) mmol/L],LDL-C [(4.11 ±0.79)mmol/L vs (3.02 ±0.81) mmol/L and (2.51 ±0.70)mmol/L] and TG [2.10(1.53,2.54) mmol/L vs 1.62(1.26,2.00) mmol/L and 1.35(1.10,1.86)mmol/L]at week 4 and 12 post-treatment in the per protocol set 55 subjects with DM were significantly reduced (all P values ＜ 0.05 ) ; 33.3％ of subjects at high risk and 10.0％ of subjects at very high risk had achieved a TC target value; 55.6％ of subjects at high risk and 40.0％ of subjects at very high risk had achieved a LDL-C target value.Conclusion Pitavastatin has a safe effect on blood glucose and it could be used to treat diabetic patients combined with hypercholesterolemia in China.

Es la pitavastatina una estatina más o un nuevo fármaco ventajoso? / Is pitavastatin just another statin or does it offer new advantages?

Hoy en día, disponemos de 7 estatinas. La pitavastatina, la estatina más nueva, parece tener ventajas significativas para el paciente que no ha tolerado otras estatinas. Además, causa una menor disminución de la coenzima Q-10 que puede resultar en un riesgo menor de miopatía. La pitavastatina no depende del citocromo P450 para su metabolismo y esto disminuye el riesgo de alteraciones metabólicas; y existe la posibilidad de un mayor aumento en la lipoproteína de alta densidad, en comparación con otras estatinas. Su uso parece justificado en algunas circunstancias y es posible que el fármaco tenga un nicho único en la disminución del riesgo cardiovascular.

There are currently 7 statins available in clinical practice. Pitavastatin is the newest statin and it appears to have significantadvantages for the patient who has not tolerated other statins. With pitavastatin, there is a smaller decrease in coenzymeQ-10 which may diminish the risk of myopathy. Also, pitavastatin does not depend on cytochrome P450 for its metabolismand this decreases the risk for metabolic alterations. In addition, pitavastatin offers the possibility of a larger increase inhigh density lipoproteins. Therefore, its usage appears justified in certain circumstances and it appears that pitavastatinmay have a unique niche in decreasing cardiovascular risk.

Prospective Study to Evaluate the Efficacy and Safety of Pitavastatin in Patients with Risk Factor of Cardiovascular Disease(PEACE Study)

BACKGROUND AND OBJECTIVES: Pitavastatin, a recently approved synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is known to effectively treat hypercholesterolemia. The goal of this study was to investigate the efficacy and safety of pitavastatin in hyperlipidemic Korean patients with coronary risk factors. SUBJECTS AND METHODS: This was an 8-week, prospective, multicenter, open-label clinical trial. The study subjects were hyperlipidemic Korean patients (triglyceride 130 mg/dL, age; 45-75 years) with at least two coronary risk factors. After a 2-week wash out period, the eligible subjects were given 2 mg of pitavastatin once daily for 8 weeks. In the case of the patients with LDL-cholesterol > or = 100 mg/dL after the first 4 weeks of treatment, the dose of pitavastatin was increased to 4 mg per day for the remaining 4 weeks. RESULTS: Of the 131 patients initially enrolled, 105 completed the study. Among the lipid profiles, the total cholesterol, triglyceride, and LDL-cholesterol levels showed a significant reduction with mean reduction rates of -30.66%, -23.92%, and -41.06%, respectively, after 8 weeks. Interestingly, the HDL-cholesterol level was significantly increased in the subjects with a low HDL-cholesterol level (HDL-cholesterol < 40 mg/dL) after 8 weeks of therapy (35.28+/-4.38 mg/dL to 40.39+/-6.45 mg/dL, 15.9%, p=0.001). The proportions of patients who achieved the LDL-cholesterol goal of the National Cholesterol Education Program Adult Treatment Panel III were 72.5% (37/51), 93.6% (44/47), and 100.0% (7/7) for the patients with goals of 100 mg/dL, 130 mg/dL, and 160 mg/dL, respectively. Five patients had mild adverse drug events, such as fatigue, itching, myalgia, and anorexia. No significant abnormalities were detected in the laboratory tests, including the liver function test and creatinine kinase level. CONCLUSION: The HMG-CoA reductase inhibitor, pitavastatin, was highly effective and generally well tolerated with an acceptable safety profile in hyperlipidemic Korean patients with coronary risk factors.