Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial / 世界急诊医学杂志（英文）

@#BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the “Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome” study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Development Of Microemulsion Formulation For Oral Delivery Of Rosuvastatin Calcium

The purpose of conducting this study was to prepare an oral microemulsion formulation of Rosuvastatin calcium (RC) to improve its water solubility. Oil in water microemulsion was formulated using Oleic acid, Tween 80 and Polyethylene Glycol-400(PEG-400) as oil, surfactant and co-surfactant, respectively. The ideal proportion of surfactant: co-surfactant (Smix) was chosen by constructing pseudoternary diagrams. The microemulsion formulations which proved to be stable after thermodynamic stability testing were further evaluated for physical characteristics. Selected formulations were evaluated for droplet size, zeta potential, polydispersity index, viscosity and % drug content. The results were suggestive that optimized microemulsion formulation (F2) was thermodynamically stable and clear having a droplet size of 74.29 nm and zeta potential of -18.44. In vitro dissolution study for optimized microemulsion was performed using a dialysis bag method and cumulative % drug release was determined. The result from the release study was indicative of improved solubility of Rosuvastatin calcium which may serve to boost up the oral bioavailability of drug.

Synthesis of the Related Substances of Rosuvastatin / 中国药学杂志

OBJECTIVE: To synthesize three related substances of rosuvastatin and establish its standard quality control system. METHODS: t-Butyl-6-[(1E)-2-[4-(4-fluorophenyl)-6-isopropanyl-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-acetate (1a) was converted into the de-ketal compound 1b, then the latter underwent hydrolysis to get 1c. Finally, N-[4-(4-fluorophenyl)-6-isopropanyl-5-[(1E)-2-[(2S, 4R)-4-hydroxyl-6-oxo-2H-pyran-2-ethenyl]-2-pyrimidinyl]-N-methyl methane sulfonamide (impurity 1) was obtained through intramolecular dehydration. Meanwhile, (3R, 5S, 6E)-7-[4-(4-fluoropheny-1)-6-isopropanyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-yl]-3,5-dihydroxy-6-heptenoic acid (impurity 2) was prepared from compound 1b via oxidation with DDQ, reduction with tetramethylammonium triacetoxyborohydride, followed by hydrolysis. (3R, 6E)-7-[4-(4-fluorophenyl)-6-isopropanyl-2-[methyl(methylsulfonyl) amino]-5-pyrimidinyl]-3-hydroxy-5-oxo-6-heptenoic acid (impurity 3) was synthesized through oxidation of compound 1c with DDQ. RESULTS: The structures of three impurities were confirmed by 1H-NMR and MS. CONCLUSION: The synthesized three target compounds can be used as references for the quality control of rosuvastatin calcium.

Effects of ezetimibe and rosuvastatin on the expression of Caveolin-1 mRNA in smooth muscle derived foam cells / 中国医师杂志

Objective To investigate the influence of ezetimibe combined with rosuvastatin on expression of Caveolin-1 in smooth muscle derived foam cells induced by oxidized low density lipoprotein (oxLDL).Methods The rat thoracic aortic smooth muscle cells (VSMCs) were selected from generations 3-5 in logarithmic growth cycle.The rat vascular smooth cells were induced using oxidized low density lipoprotein(ox-LDL 50 μg/ml for 48 h) to establish foam cell model.The normal cultured rat thoracic aortic smooth muscle cells were used as blank control group.Foam cells were divided into foam cell group,different concentrations of ezetimibe group,different concentrations of rosuvastatin group,combination group.The foam cells were incubated with different doses of ezetimibe (3.0,10.0,30.0 μmol/L) or rosuvastatin (0.1,1.0,5.0 μmol/L) for 24 h,or cultured with rosuvastatin 5.0 μmol/L + ezetimibe 30.0 μmol/L in combination groups.Oil red O staining was used to identify foam cell models.The expression of Caveolin-1 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR).Results Compared with blank control group,the mRNA expression of Caveolin-1 in foam cell group were decreased significantly [(0.248 7 ± 0.042 0) vs (1.004 1 ± 0.017 1),P ＜ 0.05].Compared with foam cell group,the mRNA expression of Caveolin-1 was increased in a dose-dependent manner in ezetimibe group and rosuvastatin group [(0.371 3 ±0.025 2),(0.489 8 ±0.027 9),(0.726 1 ±0.029 1) vs (0.248 7 ±0.042 0);(0.460 2±0.022 8),(0.623 7 ±0.028 8),(0.751 8 ±0.043 1) vs (0.248 7 ±0.042 0),P ＜0.05].Compared with the ezetimibe (30.0 μmol/L) and the rosuvastatin (5.0 μmol/L),the mRNA expression of Caveolin-1 in combined group were increased,the difference was statistically significant [(0.726 1 ±0.029 1),(0.751 8 ± 0.043 1) vs (0.937 6 ± 0.029 7),P ＜ 0.05].Conclusions Ezetimibe and rosuvastatin can promote the reverse transport of cholesterol (RCT) in smooth muscle derived foam cells by upregulating expression of Caveolin-1 mRNA.And the combination of ezetimibe (30.0 μmol/L) and rosuvastatin (5.0 μmol/L) has more significant effect.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

A Case Report of Gynecomastia Due to Rosuvastatin

Gynecomastia is a common benign disease characterized by the progressive enlargement of the glandular tissue of the male breast due to an imbalance between the levels of estrogen and androgen in the blood. The etiology may vary and may be physiological, pharmacological, pathological, or even idiopathic. Among men, drug-induced gynecomastia may account for 10% to 20% of cases. The literature contains six case reports of rosuvastatin-induced gynecomastia. Withdrawal of statin or switching to a less potent statin can lead to symptom improvement and avoidance of unnecessary tests and patient anxiety. A 62-year-old male patient developed unilateral gynecomastia after 13 months of rosuvastatin therapy. After switching to a different statin (pravastatin), his symptoms improved within 2 months. Thus, clinicians should be aware of the possibility of occurrence of gynecomastia when statins are prescribed.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Effects of Rosuvastatin Calcium at Different Doses Combined with Basic Treatment in Elderly Patients with Unstable Angina Pectoris / 中国药师

Objective:To observe the effects of rosuvastatin calcium at different doses combined with the basic treatment in elderly patients with unstable angina pectoris ( UAP) , and investigate the influence on the serum inflammatory factors .Methods:Totally 82 ca-ses of elderly patients with UAP were divided into the low dose group and the high dose group randomly .In addition to the basic treat-ment, the low dose group was given rosuvastatin calcium tablets 10mg, once per night, and the high dose group was given rosuvastatin calcium tablets 20 mg, once per night .The serum inflammatory factors and blood lipid levels of the two groups before the treatment and after 3-months treatment were compared .The therapeutic effect , frequency and duration of attack and the incidence of adverse events of the two groups were evaluated .Results:After the treatment , the levels of TC , TG and LDL-C in both groups significantly decreased , and that of HDL-C increased (P<0.05), and the blood lipid indexes in the high dose group were better than those in the low dose group (P<0.05).The levels of TNF-α, IL-6 and TGF-β1 decreased significantly after the treatment (P<0.05), and level of these indexes in the high dose group were much lower than that in the low dose group (P<0.05).The total effective rate in the high dose group was 95.43％, which was much higher than that (77.50％) in the low dose group (P<0.05).The frequency and duration of angina pectoris in the high dose group were both lower than those in the low dose group (P<0.05).The incidence of adverse events in the two groups showed no statistically significant difference (P>0.05).Conclusion:High dose rosuvastatin calcium combined with the basic treatment can effectively improve the blood lipid levels and serum inflammatory factors in the elderly patients with UAP , which exhibits good clinical curative effect .

Effect of rosuvastatin calcium combined with clopidogrel and aspirin on prevention of cerebral infarction in elderly patients with transient ischemic attack and the effects on blood lipids and platelets / 中国生化药物杂志

Objective To study the effect of rosuvastatin calcium combined with clopidogrel and aspirin on preventing cerebral infarction in elderly patients with transient ischemic attack, and the influence on blood lipid and platelet.Methods 80 elderly patients with TIA were treated in Haiyan people's hospital from September 2014 to May 2017.All the patients were randomly divided into the observation group and the control group with 40 cases in each group.The control group were treated with clopidogrel and aspirin, and the observation group was treated with rosuvastatin calcium combined with clopidogrel and aspirin.The effect of cerebral infarction prevention, blood lipid and platelet change were compared between the two groups.Results Cerebral infarction incidence was 5% in the observation group, the incidence of adverse reactions was 10%, which were significantly lower than 22.5% and 17.5% in the control group, the differences were statistically significant (P<0.05).Compared two groups of patients with blood lipid levels after the treatment, the indicators of the observation groupTC (4.89±1.13) mmol/L、TG (1.04±1.02) mmol/L、LDL-C (2.62±1.22) mmol/L was significantly lower than the control group (5.57±1.20) mmol/L、(1.58±1.06) mmol/L、(3.39±1.24) mmol/L, with statistical significance (P<0.05).After treatment, PT (16.88±1.97), APTT (46.23±4.22) in the observation group were longer than (14.01±2.02) (38.21±3.99) in the control group, PLT (150.44±9.87) in the observation group is lower (165.82±9.71) in the control group, the differences were statistically significant (P<0.05).Conclusion Rosuvastatin calcium combined with clopidogrel and aspirin has a significant effect on the prevention of elderly patients with transient ischemic attack of cerebral infarction, which can reduce the blood lipid level, prolong PT, reduce PLT, APTT, and has high value in clinical application.

Effects of rosuvastatin calcium on bone mineral density in patients with type 2 diabetes mellitus complicated with osteoporosis and carotid atherosclerotic plaque / 中国综合临床

Objective To investigate the effects of rosuvastatin calcium on bone mineral density and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus complicated with osteoporosis.Methods Eighty-two T2DM patients with osteoporosis were randomly divided into two groups,41 cases in the treatment group and 41 cases in the control group.The control group received routine treatment,including insulin and Caltrate D treatment.The observation group was treated with rosuvastatin calcium 10 mg 1 time/d orally,on the basis of the routine treatmentv.The two groups were treated for 12 weeks.After treatment,the blood glucose level,bone mineral density and carotid atherosclerotic plaques were compared.Results After treatment,the levels of blood sugar,FBG ((7.2±0.4) mmol/L),2 hBG ((9.2±0.6) mmol/L),HbAlc ((7.2±0.4) mmol/L) in the observation groups were lower than those before treatment ((9.6±0.5) mmol/L,(12.3±0.6) mmol/L,(9.8±0.7) mmol/L,t=24.0,23.39,20.65,P0.05),the BMD of femoral neck in the observation group after treatment was higher than that in the control group (t=0.842,P0.05).The differences between the observation group and the control group after treatment were statistically significant (t=0.534,0.645,P<0.05).Conclusion Rosuvastatin calcium can effectively improve the curative effect of type 2 diabetes mellitus in patients with osteoporosis and improve bone mineral density and carotid atherosclerotic plaques.

Efficacy of pushen capsule on blood lipid and atherosclerosis in patients with ischemic stroke / 天津医药

Objective To explore the efficacy of pushen capsule on blood lipid and atherosclerosis in patients with ischemic stroke.Methods One hundred and twenty patients with ischemic stroke were randomly divided into three groups,treatment group (pushen capsule and rosuvastatin calcium),control group-1 (pushen capsule) and control group-2 (rosuvastatin calcium).There were 40 patients for each group.The course of treatment was 6 months.Data of serum total cholesterol (TC),triacylglycerol (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),homocysteine (Hcy),high sensitive C reactive protein (hs-CRP),nitric oxide (NO),endothelin-1 (ET-1),the number and size of carotid plaques,and changes of intima-media thickness (IMT) were detected before and after treatment in three groups.The incidences of adverse cerebrovascular events and adverse events were observed in the three groups.And the therapeutic effects for dyslipidemia were evaluated in three groups.Results The treatment indicators were obviously improved after treatment in three groups (P ＜ 0.05).There were no significant differences in treatment indicators before treatment between three groups.The levels of TG and NO increased,the level of LDL-C,the size and thickness of carotid plaques decreased after treatment in control group-2 than those of control group-1.Levels of TC,LDL-C,Hcy,hs-CRP,ET-1,IMT,and the number,size and thickness of carotid plaques were significantly lower in treatment group than those of control group-1 (P ＜ 0.05),and the level of NO was higher in treatment group than that of control group-1 (P ＜ 0.05).Compared with control group-2,levels of TG,LDL-C,hs-CRP and the number,size and thickness of carotid plaques were significantly lower,and levels of HDL-C and NO were significantly increased in treatment group (P ＜ 0.05).There were no significant differences in the incidences of adverse drug reactions and adverse cerebrovascular events between the three groups (P ＞ 0.05).The total effective rate was higher in treatment group than that of control group-1 (P ＜ 0.05).There were no significant differences in total effective rates between treatment group and control group-2,and between control group-2 and control group-1 (P ＞ 0.05).Conclusion Pushen capsule combined with rosuvastatin calcium can obviously improve blood lipid metabolism in patients with ischemic stroke,which shows obvious antiatherosclerosis effect and good safety.

Effect of warm needling plus oral medication on blood lipids in cerebral infarction patients / 针灸推拿医学（英文版）

Objective:To observe the effect of warm needling plus oral administration of rosuvastatin calcium tablets on blood lipids in cerebral infarction patients. Methods:A total of 125 eligible cases were randomly allocated into group A (n=42), group B (n=40) and group C (n=43). Cases in group A received warm needling plus oral administration of rosuvastatin calcium tablets, cases in group B received warm needling, whereas cases in group C received oral administration of rosuvastatin calcium tablets. Results:After treatment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) all dropped obviously in the three groups, with significant differences (allP0.05). After treatment, the changes of TC, TG and LDL-C in group A were significantly different from those in group B and group C (allP0.05). There were no between-group differences in HDL-C among the three groups (allP>0.05); the modified BI scores in groupA and groupB were significantly higher than that in group C (bothP0.05).After treatment, the total effective rate was significantly higher in group A than that in group B and group C (bothP0.05). Conclusion:Warm needling and oral administration of rosuvastatin calcium tablets both can adjust blood lipids effectively in cerebral infarction patients with a similar therapeutic efficacy, while the effect gets better based upon combining both methods; acupuncture-moxibustion plays an important role in the recovery of nerve functions in cerebral infarction patients.

Effects of NOS1AP Gene Polymorphism on Lipid-regulating Response of Rosuvastatin Calcium / 中国药房

OBJECTIVE:To investigate the effects of NOS1AP rs12742393 A/C gene polymorphism on lipid-regulating re-sponse of rosuvastatin calcium. METHODS:Two hundred and tuirty six patients with coronary heart disease(CHD)were selected from cardiology department of our hospital during Jan. 2014-Jun. 2015,and then given rosuvastatin calcium and other symptomatic treatment for 12 weeks. Polymorphism of NOS1AP rs12742393 A/C was detected by PCR-RFLP. The levels of TG,TC,HDL-C and LDL-C were detected by photoelectric colorimetry before treatment and 4,12 weeks after treatment. The serum relationship of genotype with the level of blood lipid was analyzed. RESULTS:Among 236 CHD patients,there were 131 cases of AA genotype (55.5%),98 cases of AC genotype(41.5%) and 7 cases of CC genotype(3.0%);genotype and allele frequencies met the Har-dy-Weinberg balance(P>0.05). There were 132 patients with normal blood lipid and 104 patients with hypercholesterolemia;there was statistical significance in genotype and allele frequencies (P0.05). 4th and 12th week after treatment,the levels of TG,TC and LDL-C in different genotypes were all de-creased significantly;4th week after treatment,the level of LDL-C in AC+CC genotype was significantly lower than AA genotype, and the change compared to before treatment was significantly more than AA genotype,with statistical significance (P0.05). CONCLUSIONS:NOS1AP rs12742393 A/C gene polymorphism is associated with CHD complicated with hypercholesterolemia;the C allele of NOS1AP rs12742393 may strengthen the response of CHD patients with hy-percholesterolemia to rosuvastatin calcium through influencing the level of LDL-C.

Comparison between Atorvastatin and Rosuvastatin in Renal Function Decline among Patients with Diabetes

BACKGROUND: Although the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. We aimed to investigate whether, and which, statins affected renal function in Asian patients with diabetes. METHODS: We enrolled 484 patients with diabetes who received statin treatment for more than 12 months. We included patients treated with moderate-intensity dose statin treatment (atorvastatin 10 to 20 mg/day or rosuvastatin 5 to 10 mg/day). The primary outcome was a change in estimated glomerular filtration rate (eGFR) during the 12-month statin treatment, and rapid renal decline was defined as a >3% reduction in eGFR in a 1-year period. RESULTS: In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs (from 80.3 to 78.8 mL/min/1.73 m² for atorvastatin [P=0.012], from 79.1 to 76.1 mL/min/1.73 m² for rosuvastatin [P=0.001]). A more rapid eGFR decline was observed in the rosuvastatin group than in the atorvastatin group (48.7% vs. 38.6%, P=0.029). Multiple logistic regression analyses demonstrated more rapid renal function loss in the rosuvastatin group than in the atorvastatin group after adjustment for other confounding factors (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.42). CONCLUSION: These results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin.

HPLC method with correction factor for determination of related substances in compound ezetimibe and rosuvastatin calcium tablets / 中国药学杂志

OBJECTIVE: To establish the self contrast and correction factor method for the content determination of the related substances in compound ezetimibe and rosuvastatin calcium tablets simultaneously. METHODS: RP-HPLC method was adopted. The determination was performed on Kromasil 100-5 C18 Dimensions column (4.6 mm × 250 mm, 5 μm) with mobile phase A consisting of methanol-acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (10:30:60) and mobile phase B consisting of tetrahydrofuran-acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (10:50:40) at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 242 nm. The injection volume was 20 μl. The slope of linear equation was used to determine the correction factors between ROS impurities 1, 2, 3, EZT impurities 1, 2, 3, 4, 5, 6, 7 and ezetimibe or rosuvastatin calcium. The relative retention time was used to determine the positions of impurities. RESULTS: The relative retention time of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 to rosuvastatin calcium was 1.5, 1.9, 2.1, 1.1, 1.7, 2.5, 2.6, 2.8, 2.9, 3.0, and 4.0, respectively. The correction factors of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 were 1.1, 1.1, 1.0, 1.0, 1.3, 1.1, 1.0, 1.3, 1.4, 0.5, and 1.0, respectively. The content of ROS impurity 4 was 0.15% in three batches of samples, the other impurities were less than 0.1%, and the contents of total impurities were 0.27%, 0.27%, and 0.26%, respectively. CONCLUSION: The method is simple, efficient, and accurate for analyzing the related substances in compound ezetimibe and rosuvastatin calcium tablets.

Effect of different doses of rosuvastatin Calcium in the treatment of coronary heart disease complicated with hyperlipemia and its influence on blood lipid level / 中国基层医药

Objective To investigate the effect of different doses of rosuvastatin Calcium in the treatment of coronary heart disease complicated with hyperlipemia and its effect on blood lipid level.Methods 100 patients with coronary heart disease complicated with hyperlipemia were randomly divided into the three groups according to the number table methods,the patients in group A received rosuvastatin Calcium 5mg/d,group B was given 10mg/d, group C was given 20mg/d.A treatment course was 4 weeks,and continuous treatment lasted 3 courses.The effects after treatment and serum TC,TG,LDL-C and HDL-C levels before and after treatment of the three groups were compared,and the occurrence of adverse reactions in the three groups of patients was recorded.Results The effective rate of C group in the treatment of coronary heart disease was 87.9%,the effective rate in the treatment of hyperlipi-demia was 93.9%,which were significantly higher than those in group A and group B (χ2 =6.54,P<0.05 );The serum TC,TG,HDL-C and HDL-C levels of three groups after treatment were significantly improved compared with before treatment,and which in C group were improved better than the other two groups(F=5.45,P<0.05);There was no significant adverse reactions in the three groups during treatment.Conclusion Large dose rosuvastatin Calci-um has a significant therapeutic effect in treatment of coronary heart disease complicated with hyperlipemia,which can effectively regulate blood lipid levels,with no obvious adverse reaction and high security,which is worthy of clinical application.

Investigation of formulation, preparation and stability of rosuvastatin calcium tablets / 第二军医大学学报

Objective To explore the formulation and preparation technique of rosuvastatin calcium tablets with satisfactory stability and reproducibility. Methods Using suitable formulations, we prepared the rosuvastatin calcium granulates by high shear mixer and fluid bed separately, and compared their influences on the granulate properties, tablet characteristics and dissolution. The reproducibility of formulation and preparation technique was investigated. Furthermore, the factors affecting the formulation were also investigated. Results Compared with the fluid bed, granulation using high sheer mixer was more suitable for preparing rosuvastatin calcium granulates. The selected formulation and preparation technique yielded 3 batches of rosuvastatin calcium tablets which met the quality requirement. The tablets had a comparable dissolution profiles to "Crestor " of AstraZeneca. The stability of rosuvastatin calcium was largely affected by the strong light, high humidity and high temperature. Conclusion The optimized formulation and preparation technique have good reproducibility for preparing rosuvastatin calcium tablets, which have good stability.

Desarrollo y validación de un método analítico indicativo de estabilidad por HPLC para la cuantificación de Rosuvastatina Cálcica / Development and validation of a stability indicating analytical HPLC method for the quantification of Rosuvastatin Calcium

En este trabajo, fue desarrollado y validado un método indicador de estabilidad por cromatografía líquida, para ser aplicado al estudio cinético de Rosuvastatina Cálcica en diferentes valores de pH y temperatura. Las condiciones cromatográficas seleccionadas fueron: columna C18, 50 x 4.6 mm y 3,5 µm de tamaño de partícula; fase móvil MeOH: Agua-0.1%TFA, temperatura de la columna de la columna 25 ° C, y velocidad de flujo 1 mL/min. El método validado presentó una adecuada repetibilidad y precisión intermedia y una recuperación superior al 98%. Por otra parte, el método fue lineal en el rango de 10 a 150 ppm. En condiciones ácidas, fueron identificados tres posibles productos de degradación como: Rosuvastatina Lactona, Rosuvastatina Anti-isómero y Rosuvastatina Lactona Anti-isómero y en condiciones de degradación con la luz se identificaron dos posibles productos mayoritarios. El método validado puede ser empleado en estudios de estabilidad y de degradación cinética del fármaco.

In this work, a liquid chromatography stability-indicating method was development and validated to be applied at study the hydrolytic behavior of Rosuvastatin Calcium in different pH values and temperatures. The selected chromatographic conditions were a column C18 50 x 4.6 mm and 3.5 µm. The mobile phase was Methanol: Water-1%TFA; 25°C column temperature and flow rate 1 mL/min. The validation method exhibited an adequate repeatability and intermediate precision and a recovery higher than 98%. Furthermore, the method was lineal in range of 10 to 150 ppm. Under acidic conditions, three degradation products possible were identified as Rosuvastatin lactone, Rosuvastatin anti-isomer and Rosuvastatin lactone anti-isomer, with light were identified two major decomposition products. The validated method can be used in the stability studies and drug degradation kinetics.

The effect of rosuvastatin calcium on vascular endothelial function, tumor necrosis factor-α and interleukin-1 in hyperlipidemia patients / 中国医师进修杂志

Objective To observe the effect of rosuvastatin calcium on lipid,vascular endothelial growth factor (VEGF),nitric oxide (NO),tumor necrosis factor (TNF)-α and interleukin (IL)-1 in hyperlipidemia patients.Methods One hundred and twenty-seven hyperlipidemia patients were randomly divided into two groups.Patients in the study group included 72 patients which were given rosuvastatin calcium 10 mg and enteric-coated aspirin 100 mg,orally,once a day for 8 weeks.The control group included 55 patients which were only given enteric-coated aspirin 100 mg,orally,once a day for 8 weeks.The change of lipid,VEGF,NO,TNF-α and IL-1 was observed before and after treatment.Results Before treatment,the level of total cholesterol(TC),triglyceride (TG),low density lipoprotein-cholesterol (LDL-C),high density lipoprotein-cholesterol (HDL-C),VEGF,NO,TNF-α and IL-1 in two groups had no significant difference (P ＞ 0.05).After treatment,the level of TC,TG,LDL-C,TNF-α and IL-1 in study group were significantly lower than those in control group [(4.410 ± 0.688) mmol/L vs.(6.491 ± 0.744) mmol/L,(1.762 ± 0.834) mmol/L vs.(2.632 ± 0.792) mmol/L,(2.256 ± 0.347) mmol/L vs.(4.544 ± 0.493) mmol/L,(41.14 ± 5.41) ng/L vs.(71.34 ± 6.76) ng/L,(0.22 ± 0.18) μ g/L vs.(0.42 ± 0.23) μ g/L] (P ＜ 0.05).The level of HDL-C,VEGF and NO in study group were significantly higer than those in control group [(1.807 ± 0.730) mmol/L vs.(1.432 ± 0.514) mmol/L,(564.86 ± 120.02) ng/L vs.(451.23 ± 100.72) ng/L,(42.39 ± 6.71) μ mol/L vs.(33.65 ± 6.24) μ mol/L](P＜ 0.05).No adverse reaction occurred in two groups.Conclusions Rosuvastatin calcium can obviously decrease the level of lipid,elevate the expression of VEGF and NO,and reduce the expression of TNF-α and IL-1.Rosuvastatin calcium can improve vascular endothelial function obviously in hyperlipidemia patients.

Efficacy observation of rosuvastatin treatment on the patients with hyperlipidemia and hypertension / 中华老年医学杂志

Objective To analyze the efficacy of rosuvastatin on the patients with hyperlipidemia and hypertension.Methods From March 2011 to June 2012,112 cases with hyperlipidemia and hypertension in our hospital were enrolled in this study.Patients were randomly divided into treatment group and control group (56 patients,each).Patients in control group were treated with oral amlodipine 5 mg/d.Patients in treatment group were treated with oral rosuvastain 10 mg/d and oral amlodipine 5 mg/d.One month after the treatment,the levels of blood pressure,total cholesterol (TC),tryglyceride (TG),low density liporotein (LDL-C),high density lipoprotein cholesterol (HDL-C),high sensitivity C-reactive protein (hsCRP) were determined.The occurrence of adverse effects were observed.Results One month after treatment,systolic blood pressure and diastolic blood pressure were significantly decreased in both two groups compared with pre-treatment [Control group:(135.2±9.51)mm Hgvs.(59.2±7.3)mm Hg,(88.8±5.2)mm Hg vs.(99.5±8.3)mm Hg,t=4.95,2.87; Treatment group:(130.2±5.5)mm Hg vs.(160.3±9.3)mm Hg,(86.7± 10.2)mm Hg vs.(99.7±8.3)mm Hg,t=5.03,2.94,all P＜0.01],but more declines were found in treatment group than in control group(t=3.96,3.42,both P＜0.001).The levels of LDL-C,TG and TC were significantly decreased in both two groups compared with pre-treatment [Control group:(2.64±0.72)mmol/L vs.(3.97±0.84)mmol/L,(1.89±0.25)mmol/L vs.(2.56±0.45)mmol/L,(4.23±0.56)mmol/L vs.(7.36±0.48)mmol/L,t=2.58,3.03,2.36,P=0.013,0.004,0.022;Treatment group:(1.75 ± 0.68) mmol/L vs.(3.85 ± 0.79) mmol/L,(1.71 ± 0.18) mmol/L vs.(2.63±0.42)mmol/L,(3.18±0.47)mmol/L vs.(7.20±0.56)mmol/L,t=2.77,3.16,2.59,P=0.008,0.003,0.012,respectively],but more declines were observed in treatment group than in control group(t=6.73,4.37,10.70 respectively,all P＜0.05).The HDL-C concentrations were increased in both two groups compared with pre-treatment [Control group:(0.97±0.26)mmol/L vs.(0.75±0.31)mmol/L,t=2.89,P=0.006; Treatment group:(1.09±0.23)mmol/L vs.(0.72±0.24)mmol/L,t=3.01,P=0.004],but more increment were observed in treatment group than in control group(t=2.59,P＜0.05).The hsCRP concentration was significantly reduced in treatment group compared with pre-treatment [(1.32±0.17) mg/L vs.(4.97±0.13) mg/L,t=4.40,P＜0.001].There were no significant differences in liver and kidney function between the two groups.Serious adverse effects were not found.Conclusions Rosuvastatin combined with routine antihypertensive therapy can effectively decrease the levels of serum LDL-C,TG,hsCRP; increase serum HDL-C concentration and blood pressure can be effectively controlled.