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A 50-year-old female presented with bilateral cervical arteriosclerosis and right-sided plaque formation,after 25 d of treatment with rosuvastatin calcium tablets(20 mg,po,qn),the patient developed temporomandibular joint dislocation,the adverse reactions occurred again after giving manipulative repositioning.The patients were healthy,had no history of trauma and related diseases in stomatology,no history of drug allergy,patients did not open their mouth loudly at the onset of the disease,no external factors affecting the use of drugs during the combined use of other drugs.It was considered"very likely"that the dislocation of the jaw joint was caused by rosuvastatin calcium tablets.The patients were followed up for 3 months after the treatment of manipulative repositioning and other treatments,did not have any further dislocation of the temporomandibular joint dislocation.It is suggested that when using rosuvastatin calcium in clinical practice,attention should be paid to strengthening drug observation to ensure drug safety.
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Background: In country like India, therapy with rosuvastatin recommended dose may cost between Rs. 400.00 and Rs. 800.00/month. The lower and middle income groups of Indian society are rapidly becoming major sufferers of cardiovascular disease, among all non-communicable diseases, the economic burden of rosuvastatin therapy may be substantial for this large section of population. Aims and Objectives: The aim of the study was to study the cost-effectiveness of rosuvastatin on alternate day versus daily dosing regimen in hyperlipidemia patients. Materials and Methods: The research was carried out at MNR Medical College and Hospital’s department of pharmacology in association with general medicine. According to the inclusion criteria, 50 patients aged 30–60 years of both sexes were included in this prospective open label trial. The research lasted 6 weeks. All the participants were included in study after obtaining the informed consent and approval of the Institutional Ethics Committee was obtained before enrolment of participants. All patient data were obtained using a pre-designed proforma and put into an excel spreadsheet. Results: A total of 42 patients are included with 16 females (38%) and 26 men (62%). Cost of daily rosuvastatin for 6 weeks is Rs. 1087.80 (yearly daily dosing expenses 9453.50%) accounting for mean reduction of LDL-cholesterol (LDL-C) of 33.50% and for alternate day rosuvastatin for 6 weeks is 543.90% (yearly alternate day dosing expense 4713.80%) accounting for mean reduction of LDL-C of 31%. Conclusion: Treatment with alternate day dose of rosuvastatin is comparably cost-effective when compared to currently practicing daily dose rosuvastatin therapy.
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Background: The common cause of mortality in India is related to complications of cardiovascular disease which has direct relation with the hyperlipidemia, diabetes mellitus, and hypertension. Rosuvastatin more efficacious than other statins in lesser dosage and having good safety profile. Aim and Objective: The present study was undertaken to evaluate the safety, efficacy of rosuvastatin 10 mg daily dose versus alternate day dose in hyperlipidemia patients. Materials and Methods: A total of 50 individuals with hyperlipidemia were selected in this prospective open label research. Patients were grouped as Group D with rosuvastatin daily dose and Group A with alternate day dose. Fasting plasma lipid profile was assessed in both groups on the 1st, 4th, and 6th weeks. Results: There is significant reduction in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and elevation of high-density lipoprotein (HDL) after 4 weeks and 6 weeks of the treatment in both the groups compared to baseline. The mean percentage reduction of total cholesterol was by 24% and 21.60% (P < 0.05) in Group D and Group A, respectively. The mean percentage reduction of LDL-C was by 33.50% and 31% (P < 0.05) Group D and Group A, respectively. The mean percentage improvement of HDL-cholesterol was by 19.89% and 17.09% (P < 0.05) in Group D and Group A, respectively. The mean percentage of reduction of TG was by 36.70% and 41.33% (P < 0.05) Group D and Group A. Conclusion: Rosuvastatin 10 mg on alternate days had the same efficacy in lowering cholesterol levels as taking it every day, also it may be a cost-effective alternative without sacrificing therapeutic benefits or side effects.
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@#Objective To investigate clinical observation of butylphthalide soft capsules combined with rosuvastatin in the treatment of patients with acute cerebral infarction and its influence on serum Lp-PLA2,IL-18,OX40L. Methods From September 2021 to January 2022,we collected 100 patients with acute cerebral infarction who were admitted to the neurology ward and outpatient department of our hospital. These patients were randomly divided into two groups:the control group and the treatment group,with 50 patients in each group. The control group was given basic treatment and rosuvastatin (10 mg/time,1 time/d),while the treatment group was additionally given butylphthalide soft capsule (0.2 g/time,3 times/d). According to the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index,the degree of neurological deficit and ability of daily life of the two groups were evaluated before and 90 days after treatment,and the levels of serum Lp-PLA2,IL-18,OX40L were compared. Results The total clinical efficacies in the treatment group were 94.00%,higher than 80.00% in the control group(P<0.05). After 90 d treatment,NIHSS score and Lp-PLA2 level decreased,Barthel index increased,and the improvement in the treatment group was significantly better than those in the control group (P<0.05). The level of serum Lp-PLA2 was higher in patients with high NIHSS scores in the treatment group than in patients with low NIHSS scores. Before treatment,there were no significant differences between the two groups in NIHSS score,Barthel index,IL-18 levels,and OX40L levels. After treatment,there were also no significant differences between the two groups in IL-18 and OX40L levels (P>0.05). The incidence of adverse reactions in the two groups was 12.00% and 16.00%,respectively(P>0.05). Conclusion The combination of butylphthalide soft capsule and rosuvastatin has good efficacy and safety,which can significantly promote the recovery of neurological function,improve the ability of daily life,and reduce the level of serum Lp-PLA2.
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Objective:To investigate the influence of rosuvastatin combined ticagrelor on therapeutic effect,cardiac func-tion and inflammatory factor levels in patients with acute myocardial infarction(AMI).Methods:A total of 288 AMI pa-tients admitted in our hospital were randomly and equally divided into rosuvastatin group(received rosuvastatin therapy)and combined treatment group(received rosuvastatin combined with ticagrelor).After two-month treatment,therapeu-ticeffect,cardiac function,inflammatory index levels and incidence rate of adverse reaction were compared between two groups.Results:Total effective rate of combined treatment group was significantly higher than that of rosuvastatin group(96.53%v.s 86.81%,P=0.003).Compared with before treatment,there were significant improvements in cardiac function and inflammatory factor levels in two groups after treatment,P=0.001 al.l Compared with rosuvastatin group af-ter treatment,there were significant reductions in left ventricular end-diastolic diameter(LVEDd)[(44.86±5.25)mmv.s(30.94±4.02)mm],left ventricular end-systolic diameter(LVESd)[(28.83±3.02)mmv.s(21.27±2.86)mm],interventricular septal thickness(IVST)[(9.82±1.51)mmv.s(9.09±1.46)mm],levels of interleukin-6(IL-6)[(4.62±0.68)pg/mlv.s(3.85±0.59)pg/ml]and tumor necrosis factor-α(TNF-α)[(1.25±0.22)pg/mlv.s(0.93±0.18)pg/ml],and significant rise in 6 min walking distance(6MWD)[(398.63±50.58)m v.s(436.35±52.03)m]and LVEF[(54.11±6.32)%v.s(60.24±7.88)%]in combined treatment group,P=0.001 al.l There was no signif-icant difference in total incidence rate of adverse reactions during treatment between two groups,P=0.444.Conclusion:The combination of rosuvastatin and ticagrelor possesses significant therapeutic effect in the treatment of AMI patient.s It can improve cardiac function and reduce levels of inflammatory factors with good safety.
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Abstract Objective: To investigate the safety and efficacy of short-term (7-day) Dual Antiplatelet Therapy (DAPT) with intensive rosuvastatin in Acute Ischemic Stroke (AIS). Methods: In this study, patients with AIS in the emergency department of the hospital from October 2016 to December 2019 were registered and divided into the control group (Single Antiplatelet Therapy [SAPT] + rosuvastatin) and the study group (7-day DAPT + intensive rosuvastatin) according to the therapy regimens. The generalized linear model was used to compare the National Institute of Health Stroke Scale (NIHSS) scores between the two groups during the 21-day treatment. A Cox regression model was used to compare recurrent ischemic stroke, bleeding events, Statin-Induced Liver Injury (SILI), and Statin-Associated Myopathy (SAM) between the two groups during the 90-day follow-up. Results: Comparison of NIHSS scores after 21-day treatment: NIHSS scores in the study group decreased significantly, 0.273-times as much as that in the control group (Odds Ratio [OR] 0.273; 95% Confidence Interval [95% CI] 0.208-0.359; p < 0.001). Comparison of recurrent ischemic stroke during the 90-day follow-up: The therapy of the study group reduced the risk of recurrent stroke by 65% (7.76% vs. 22.82%, Hazard Ratio [HR] 0.350; 95% CI 0.167-0.730; p = 0.005). Comparison of bleeding events: There was no statistical difference between the two groups (7.79% vs. 6.71%, HR = 1.076; 95% CI 0.424-2.732; p = 0.878). No cases of SILI and SAM were found. Conclusions: Short-term DAPT with intensive rosuvastatin effectively relieved the clinical symptoms and significantly reduced the recurrent stroke for patients with mild-to-moderate AIS within 90 days, without increasing bleeding events, SILI and SAM.
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Background: The present study was aimed to evaluate the efficacy of 1.2% Atorvastatin (ATV) with 1.2% Rosuvastatin (RSV) as local drug delivery for treatment of Chronic Periodontitis (CP). Materials and Methods: Forty patients were equally divided into two groups. Group A underwent scaling and root debridement and 1.2% ATV gel (1.2 mg/0.1 mL) was placed, whereas group B received scaling and root debridement and RSV (1.2 mg/0.1 ml) was placed. Results: The results showed that both the groups had improvement in all the recorded parameters, and the results obtained were statistically significant. When comparison was made between the groups, no significant difference was obtained between atorvastatin and rosuvastatin at baseline in all recorded parameters. However, after 6 months significant improvement was recorded in CAL (Clinical attachment level) and PD (Probing depth). The plaque index (PI) and gingival index (GI) score however showed improvement, but it did not attain the level of significance. Conclusion: The present study showed improvement in clinical parameters with the use of ATV and RSV gel when used in combination with scaling and root planing (SRP) in CP patients. Patients with RSV gel showed up significantly better than the ones in which ATV gel was placed.
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@#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.
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Statins can bring some benefits to the treatment of diabetic cardiomyopathy (DCM), but the specific molecular pathway of their action is still unclear. Recent studies have shown that abnormal expression of long noncoding RNA (lncRNA) is closely related to the pathological development of DCM. To compare the degree of myocardial injury between diabetic rats treated with rosuvastatin and rats treated with conventional therapy, the therapeutic pathway and potential target of rosuvastatin on DCM was investigated. Total RNA of DCM rats was extracted and 1ncRNA microarray was prepared to screen out differentially expressed 1ncRNA and bioinformatics analysis was carried out. The results showed that 770 target genes were up-regulated and 884 were down-regulated in the treatment group compared with the model group, which were mainly related to improvement of metabolic disorder, regulation of the ratio of myocardial cells to collagen fibers, reduction of myocardial injury and exercise burden, prevention of autonomic nervous system and microcirculation diseases and change of eating habits. The signaling pathways involved are mainly concentrated in sensory pathways, signal transduction, lipid metabolism and so on. It is suggested that rosuvastatin may play a role in the treatment of DCM by regulating the participation of 1ncRNA in glucose and lipid energy metabolism and ion balance, inhibiting the process of myocardial fibrosis and improving the effect of high glucose toxicity on autonomic nervous function.
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Objective:To compare the effects of rosuvastatin and atorvastatin on coronary artery bypass grafting (CABG) on the incidence of acute kidney injury (AKI), and assess the independent risk factors of AKI.Methods:We retrospectively collected 550 patients aged 18 years or older who underwent CABG from May 2014 to May 2020. They were divided into the rosuvastatin group ( n=322), atorvastatin group ( n=125) and non statins group ( n=103) according to whether rosuvastatin or atorvastatin was routinely used before operation. Demographic data, clinical data before and after CABG and laboratory results were collected. Blood urea nitrogen (BUN), serum creatinine (Scr), creatinine clearance rate (Ccr) and incidence of postoperative AKI were compared among the three groups. Univariate analysis and binary logistic regression analysis were used to investigate the effect of statins on AKI in patients undergoing CABG. Results:Compared with preoperation, BUN showed no significant change ( P>0.05), while Scr was increased and Ccr was decreased significantly (both P<0.01); BUN in the rosuvastatin group was decreased significantly ( P<0.01), whereas Scr and Ccr had no significant change ( P>0.05); Scr in the atorvastatin group was increased significantly ( P<0.01), but there was no significant difference in BUN and Ccr ( P>0.05). BUN and Scr in the non statins group were increased significantly (both P<0.01), while Ccr was decreased significantly ( P<0.01). After operation, BUN and Scr in the rosuvastatin group and atorvastatin group were significantly lower than those in the non statins group (all P<0.01); Ccr was significantly higher than that in the non statins group ( P<0.01). BUN and Scr were not significantly different between the rosuvastatin and atorvastatin groups ( P>0.05), but Ccr was significantly higher than that in the atorvastatin group ( P< 0.05). There were significant differences in BUN, Scr and Ccr among the three groups ( χ2=48.925, 22.677 and 34.426, all P<0.01). The incidence of AKI among 550 patients was 15.1% (83/550), of which 9.6% (31/322) in the rosuvastatin group, 16.0% (20/125) in the atorvastatin group and 31.1% (32/103) in the non statins group. The incidence of AKI in the rosuvastatin and atorvastatin groups was significantly lower than that in the non statins group ( χ2=28.412, 7.282, P<0.01). Multivariate regression analysis showed that hypertension ( OR=3.555, 95% CI: 1.959-6.451, P<0.01), NHYAⅢ/Ⅳ ( OR=2.438, 95% CI: 1.187-5.008, P=0.015), and increased serum creatinine level ( OR=1.018, 95% CI: 1.003-1.032, P=0.016), and intraoperative cardiopulmonary bypass ( OR=2.936, 95% CI: 1.454-5.927, P=0.003) were independent risk factors for AKI after CABG, while preoperative conventional statin therapy ( OR=0.490, 95% CI: 0.247-0.974, P=0.042) and increased serum albumin level ( OR=0.920, 95% CI: 0.856-0.990, P=0.026) were protective factors for AKI after CABG. Conclusions:The incidence of AKI after CABG is common. Rosuvastatin or atorvastatin and increased preoperative serum albumin level can protect renal function and reduce the incidence of AKI, which are the protective factors of AKI after CABG. The hypertension, NHYAⅢ/Ⅳ, increased preoperative serum creatinine level and cardiopulmonary bypass are the independent risk factors of AKI after CABG.
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Aim To explore the biological role and related mechanism of rosuvastatin (RS) in mitochondrial damage of neurons after cerebral ischemia/reperfusion (CIR) through UCP2-SIRT3 signaling pathway. Methods Human neuroblastoma cell (SH-SY5Y cell) cerebral infarction reperfusion model (OGD/R) was established, different concentrations of RS (40 and 2. 5 (mol • L
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AIM: To study the protective effect and mechanism of rosuvastatin on cerebral ischemia-reperfusion injury. METHODS: (1) Cerebral infarction and OGD/R cell models were established to detect the effects of different concentrations of rosuvastatin on cell proliferation and apoptosis; (2) Different concentrations of rosuvastatin were used to treat OGD/R cell models and to observe rosuvastatin effects on cell morphology and expression and localization of UCP2-SIRT3 in cells; (3) UCP2 silent cell line was constructed to observe cell mitochondrial morphology and expression and localization of TOMM20 and SIRT3 molecules in cells, and to study the channels and mechanisms that play a protective role of rosuvastatin in OGD/R cell model; (4) The mitochondrial membrane potential, mitochondrial gene PGC1, Drp1 and Opa1 expression were detected to study the protective effect of rosuvastatin on mitochondria. RESULTS: (1) Rosuvastatin of different concentrations could significantly reduce OGD/R cell apoptosis and increase cell survival rate; (2) Rosuvastatin exerted cell protection by affecting the expression of UCP2 and SIRT3 in cells, thereby protecting cells from OGD/R injury; (3) Rosuvastatin affected the expression of TOMM20 by regulating UCP2, increased mitochondrial transmembrane transport and energy metabolism, enhanced mitochondrial function, and improved cell state and reduced apoptosis. CONCLUSION: Rosuvastatin inhibits mitochondrial damage of OGD/R cells by regulating UCP2/SIRT pathway, thereby exerting neuron protection.
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Objective:To observe the expressions of c-Jun N-terminal kinase (JNK), matrix metalloproteinase-9 (MMP-9) and macrophage marker MAC387 in the blood vessels of rats with vertebrobasilar dolichoectasia (VBD), and to study the therapeutic effect and mechanism of rosuvastatin on VBD.Methods:Sixty male SD rats were randomly divided into sham-operated group, VBD model group and rosuvastatin intervention group ( n=20). Elastase at 0.3 uL (1.5 U/μL) was injected into the cisterna magna of rats in the latter two groups to establish VBD models; while same volume of saline solution was given to rats in the sham-operated group. Twenty-four h after model making, 5 mg/(kg.d) rosuvastatin (once/d, for 4 weeks) was administered intragastrically into rats in the rosuvastatin intervention group, and same volume of distilled water was administered intragastrically into rats in the other 2 groups. The degrees of extension and expansion of vertebrobasilar artery were measured and compared among the 3 groups. Western blotting was used to detect the expressions of JNK and MMP-9, and immunofluorescent staining was used to detect the MAC387 expression in the vertebrobasilar artery. Results:Fourteen rats in the VBD model group and rosuvastatin intervention group, respectively, had successful model making. As compared with the sham-operated group, the VBD model group and rosuvastatin intervention group had statistically increased basilar artery diameter and basilar artery tortuosity index ( P<0.05). The expressions of JNK, MMP-9 and MAC387 in the VBD model group and rosuvastatin intervention group were significantly increased as compared with those in the sham-operated group ( P<0.05); as compared with those in the VBD model group, the expressions of JNK, MMP-9 and MAC387 in the vertebrobasilar artery of rosuvastatin intervention group were significantly decreased ( P<0.05). Conclusion:Rosuvastatin can delay VBD progress, whose mechanism may be related to the inhibition of inflammatory response.
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Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusions: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease. (AU)
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Humans , Male , Female , Acetylcysteine , Oxidative Stress , Adrenoleukodystrophy/therapy , Rosuvastatin Calcium , FibroblastsABSTRACT
The objectives of this study were to optimize the formula of the self-nanoemulsifying drug delivery system (SNEDDS)containing rosuvastatin and to evaluate its physicochemical characteristics. The solubility and compatibility ofrosuvastatin in surfactants, cosurfactants, and oil excipients were evaluated. The D-optimal experimental design,created by JMP 15 software, was used for analyzing the effects of excipients on the physicochemical characteristicsof SNEDDS to optimize the rosuvastatin SNEDDS formula. The generated nanoemulsions from Ros SNEDDS werecharacterized for droplet size, polydispersity index, and entrapment efficiency. As a result, Cremophor RH40, Capryol90, and PEG 400 were selected to develop the pseudoternary phase diagram to identify the area capable of selfforming nanoemulsion. As the percentage of rosuvastatin calcium increased from 8% to 12%, the area for optimizingthe formula of Ros SNEDDS decreased. The Ros SNEDDS prepared according to predicted formulas possessed selfemulsification to form nanoemulsion with average droplet size less than 100 nm, polydispersity index less than 0.3,and rosuvastatin entrapment higher than 90%.
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Rosuvastatin calcium is the most effective antilipidemicdrug and is called "super-statin" but it exhibits low aqueous solubility and poor oral bioavailability of about 20%. The present work aimed to develop and optimize chitosan-alginate nanoparticulate formulation of rosuvastatin which can improve its solubility, dissolution and therapeutic efficacy. Chitosan-alginate nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation and optimization was done in terms of two biopolymers, crosslinker concentrations. The chitosan-alginate nanoparticles were characterized by various techniques such as particle properties such as size; size distribution (polydispersity index); Zeta-potential measurements and Fourier transform infrared spectra respectively. The designed rosuvastatin loaded chitosan-alginate nanoparticle had the average particle size of 349.3 nm with the zeta potential of +29.1 mV, and had high drug loading and entrapment efficiencies. Fourier transform infrared spectra showed no chemical interaction between the rosuvastatin and chitosan-alginate nanoparticle upon the encapsulation of rosuvastatin within the nanoparticles. Nanoparticles revealed a fast release during the first two hours followed by a more gradual drug release during a 24h period. Hence, our studies demonstrated that the new chitosan-alginate nanoparticle system of rosuvastatin is a promising strategy for improving solubility and in turn, the therapeutic efficacy of rosuvastatin. Therefore, the rosuvastatin-loaded chitosan-alginate nanoparticles are a promising approach for the oral delivery of rosuvastatin.
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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.
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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.
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Objective: To develop a ultra performance liquid chromatography- tandem mass spectrometry(UPLC- MS/MS) method for the simultaneous determination of rosuvastatin(RT), atorvastatin(AT)and their metabolites, i.e., atorvastatin lactone (ATL), ortho- hydroxy-atorvastatin(O-AT)and para-hydroxy-atorvastatin(P-AT), in human plasma. Methods: Deuterium-labeled compounds, RT-d6, AT-d5 and P-AT-d5 were used as the internal standards(IS). The plasma samples were extracted with ethyl acetate. The chromatographic separation was achieved on a ACQUITY UPLCTM BEH C18 column(50 mm×2.1 mm, 1.7 μm)with the mobile phase of 0.2%(v/v)formic acid aqueous solution and methanol by gradient elution. The flow rate was 0.2 ml/min, and the column temperature was 40℃. Analytes were detected on a tandem mass spectrometer, equipped with an electrospray ionization source that was operated in the positive mode. The selectivity, standard curve, precision and accuracy, extraction recoveries, matrix effect, and stability were investigated. Results: The linear range of RT was 0.1-50 ng/ml with r2 =0.9977. The linear range for AT, ATL, O-AT and P-AT was 0.05-50 ng/ml with r2 =0.9997, 0.9988, 0.9923 and 0.9995, respectively. Conclusion: The established method is rapid, sensitive, accurate, specific and reliable, which is suitable for the simultaneous determination of RT, AT and their metabolites in human plasma.
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OBJECTIVE：To rapidly evaluate the effectiveness，safety and economics of rosuvastatin （RSV）in the treatment of dyslipidemia，so as to provide evidence-based support for clinical drug use. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ，CNKI，Wanfang database and CBM ，etc.，health technology assessment （HTA）related website and database were searched systematically to select HTA report ，Meta-analysis/systemic evaluation and pharmacoeconomics study about RSV versus placebo or other positive drugs in the treatment of dyslipidemia. According to the inclusion and exclusion criteria ，two researchers independently screened the literatures ，extracted and summarized the data ，then performed qualitative description of results. RESULTS ：Totally 11 Meta-analysis and 11 pharmacoeconomic studies were included ，and no relevant HTA report was retrieved. Results of the study showed that compared with the control group ，RSV could regulate dyslipidemia ，and reduce the levels of LDL-C ，TG，TC，C-reactive protein and sdLDL ；RSV could also reverse atherosclerotic plaque ，reduce all-cause mortality with good safety. In terms of economy ，compared with other statins or placebo ，RSV could prolong quality-adjusted life year，its incremental cost-effectiveness ratio is lower than the desired payment threshold ，which had more economic advantages. CONCLUSIONS：RSV is effective ，safe and economical in the treatment of hyperlipidemia.