• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.321-329
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• 2018

It was recently reported that the $C_{max}$ and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan-rosuvastatin case, simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the $T_{max}$ changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report ($C_{maxI}/C_{max}$: 2.01, $AUC_I/AUC$:1.18, $T_{max}:5h{\rightarrow}0.75h$). In the next case of cyclosporine-rosuvastatin, the simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the $CL_{int,BCRP,intestine}$ of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin-telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin-cyclosporine interaction).

• Journal of Life Science
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• v.26 no.4
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• pp.398-405
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• 2016

Statins, the inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used in treatments of hypercholesterolemia and newly known as anti-cancer effect of various cancer cells. Recently, several studies suggested that reactive oxygen species (ROS) play a critical role on cell death signaling. However, mechanism of ROS by rosuvastatin is currently unclear. This study aimed to explore the molecular mechanism of apoptosis by rosuvastatin in human prostate cancer PC-3 cells. Cell viability and apoptosis-related protein expression were measured by MTT assay and western blotting, respectively. In addition, the levels of apoptosis and ROS were analyzed. The results showed that rosuvastatin dramatically reduced cell viability in a dose- and time-dependent manner. We confirmed that rosuvastatin induced apoptosis through reduction of procaspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in PC-3 cells. In addition, rosuvastatin stimulated ROS production in a dose-dependent manner and pre-treatment with N-acetylcysteine (NAC), a ROS scavenger, significantly recovered rosuvastatin-induced ROS and apoptosis. Thus, we concluded that rosuvastain induces apoptosis through generation of ROS in human prostate cancer PC-3 cells and provides a promising approach to improve the efficacy of cancer therapy.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.54-60
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• 2008

Dyslipidemia is the multiple lipid metabolic disorders which is one of the high risk factors for the atherosclerotic diseases. It increases the morbidity and mortality and therefore, must be treated with antilipidemic agents. HMG-Co A reductase inhibitors (statins), one of many antidyslipidemic agents, have shown to be significant improvement from the various cholesterol levels. Especially, data from many comparative trials suggest that rosuvastatin is more effective than atorvastatin among many other statins. The aims of this study were to evaluate the efficacy and safety between rosuvastatin and atorvastatin in the treatment of Korean patients with dyslipidemia. Currently the Korean Society of Lipidology and Atherosclerosis based on the Korean health screening data suggests that Korean patients with dyslipidemia should be treated by the target cholesterol levels according to the Adult Treatment Panel III guidelines of the US National Cholesterol Education Program (NCEP-ATP III). We reviewed retrospectively all medical histories of the total 392 dyslipidemic patients with atorvastatin or rosuvastatin from June 1st, 2004 to August 31st, 2006 in Chungbuk National University Medical Center. Patients were classified as total 4 groups by the NCEP-ATP III Guidelines. The numbers of enrolled patients were each 5 mg atorvastatin (n=34), 10 mg atorvastatin (n=148), 5 mg rosuvastatin (n=94) and 10 mg rosuvastatin (n=82). In comparison between groups, rosuvastatin groups in the lowering LDL-C had better efficacies, and the results were each 22% (5 mg atorvastatin), 33.3% (10 mg atorvastatin), 35% (5 mg rosuvastatin) and 41.3% (10 mg rosuvastatin) with the dose relationship (P=0.000). Rosuvastatin groups also have shown to be more significantly reducing Total Cholesterol levels compared to atorvastatin groups with the no dose relationship (P=0.000). In the lowering of non-HDL cholesteroles, rosuvastatin groups showed significantly better efficacies than atorvastatin with the dose-relationship (P=0.000). Each medication groups did not demonstrate the differences in the changing of HDL cholesterol and triglyceride levels (P=0.096, 0.309, respectively). In conclusion, rosuvastatin was better efficacious than atrovastatin in reducing LDL-C Total Chol, and Tg. Therefore, rosuvastatin is a good antilipidemic agents for Korean patients with dyslipidemia and it can use to minimize the morbidity and mortality related to the cardiovascular diseases in Korean.

• Tuberculosis and Respiratory Diseases
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• v.78 no.3
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• pp.281-285
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• 2015

Statins lower the hyperlipidemia and reduce the incidence of cardiovascular events and related mortality. A 60-year-old man who was diagnosed with a transient ischemic attack was started on acetyl-L-carnitine, cilostazol, and rosuvastatin. After rosuvastatin treatment for 4 weeks, the patient presented with sudden onset fever, cough, and dyspnea. His symptoms were aggravated despite empirical antibiotic treatment. All infectious pathogens were excluded based on results of culture and polymerase chain reaction of the bronchoscopic wash specimens. Chest radiography showed diffuse ground-glass opacities in both lungs, along with several subpleural ground-glass opacity nodules; and a foamy alveolar macrophage appearance was confirmed on bronchoalveolar lavage. We suspected rosuvastatin-induced lung injury, discontinued rosuvastatin and initiated prednisolone 1 mg/kg tapered over 2weeks. After initiating steroid therapy, his symptoms and radiologic findings significantly improved. We suggest that clinicians should be aware of the potential for rosuvastatin-induced lung injury.

• Journal of Lipid and Atherosclerosis
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• v.5 no.1
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• pp.61-77
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• 2016

Objective: This study aims to analyze cost-effectiveness of two most-commonly used statins from the perspective of the Korean national health system. Methods: The scope of the analysis included rosuvastatin (5 mg, 10 mg, and 20 mg) and atorvastatin (10 mg, 20 mg, 40 mg, and 80 mg). Effectiveness was defined as percentage (%) and absolute (mg/dL) reductions of low-density lipoprotein cholesterol (LDL-C) from the baseline. They were derived from published randomized controlled studies for rosuvastatin and atorvastatin. Effectiveness was defined as reductions in LDL-C levels per mg dose of the drugs. The annual direct medical costs including drug acquisition costs and monitoring costs over the one-year time horizon were calculated for each alternative. The average cost-effectiveness ratios (ACERs) and incremental cost-effectiveness ratios (ICERs) for each statin dose were calculated. Results: The ACERs for all doses of rosuvastatin (5 mg, 10 mg, and 20 mg) were lower than those for all doses of atorvastatin (10 mg, 20 mg, 40 mg, and 80 mg). Rosuvastatin 10 mg was the most cost-effective statin for LDL-C reduction. In cost-effectiveness analyses for corresponding doses of rosuvastatin and atorvastatin, rosuvastatin was the superior strategy which suggests both higher effectiveness and lower costs than atorvastatin. However, we have to consider this analysis is highly influenced by current price of statins in each market. Conclusion: For reduction of LDL-C levels in Korean patients with dyslipidemia, rosuvastatin 10mg is the most cost-effective statin in the current Korean market.

• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.115-121
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• 2004

• Korean journal of dermatology
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• v.56 no.10
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• pp.651-653
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• 2018

• Journal of Chest Surgery
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• v.44 no.3
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• pp.208-214
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• 2011

Background: Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions. We aimed to assess the efficacy of high-dose rosuvastatin loading in patients with stable angina undergoing off-pump coronary artery bypass grafting (OPCAB). Materials and Methods: A total of 142 patients with stable angina who were scheduled to undergo surgical myocardial revascularization were randomized to receive either pre-treatment with 60-mg rosuvastatin (rosuvastatin group, n=71) or no pre-treatment (control group, n=71) before OPCAB. The primary endpoint was the 30-day incidence of major adverse cardiac events (MACEs). The secondary endpoint was the change in the degree of myocardial ischemia as evaluated with creatine kinase-myocardial band (CK-MB) and troponin T (TnT). Results: There were no significant intergroup differences in preoperative risk factors or operative strategy. MACEs within 30 days after OPCAB occurred in one patient (1.4%) in the rosuvastatin group and four patients (5.6%) in the control group, respectively (p=0.37). Preoperative CK-MB and TnT were not different between the groups. After OPCAB, the mean maximum CK-MB was significantly higher in the control group (rosuvastatin group $10.7{\pm}9.75$ ng/mL, control group $14.6{\pm}12.9$ ng/mL, p=0.04). Furthermore, the mean levels of maximum TnT were significantly higher in the control group (rosuvastatin group $0.18{\pm}0.16$ ng/mL, control group $0.39{\pm}0.70$ ng/mL, p=0.02). Conclusion: Our findings suggest that high-dose rosuvastatin loading before OPCAB surgery did not result in a significant reduction of 30-day MACEs. However, high-dose rosuvastatin reduced myocardial ischemia after OPCAB.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.275-284
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• 2024

Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy. Both rosuvastatin and ezetimibe have low bioavailability which will stand as barrier to decrease cholesterol levels, because of such depictions, formulations of this combined therapy in nanotechnology will be of a great assistance. Our study demonstrated preparations of nanoparticles of this combined therapy, showing their physical characterizations, and examined their behavior in laboratory conditions and vivo habitation. The mean particle size was uniform, polydispersity index and zeta potential of formulations were found to be in the ranges of (0.181-0.72) and (-13.4 to -6.24), respectively. Acceptable limits of entrapment efficiency were affirmed with appearance of spherical and uniform nanoparticles. In vitro testing showed a sustained release of drug exceeded 90% over 24 h. In vivo study revealed an enhanced dissolution and bioavailability from loaded nanoparticles, which was evidenced by calculated pharmacokinetic parameters using triton for hyperlipidemia induction. Stability studies were performed and assured that the formulations are kept the same up to one month. Therefore, nano formulations is a suitable transporter for combined therapy of rosuvastatin and ezetimibe with improvement in their dissolution and bioavailability.

• Korean Circulation Journal
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• v.54 no.1
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• pp.43-56
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• 2024

Background and Objectives: The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients. The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150^® (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium. Methods: A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins. The Entelon150^® group was administered 7.7 mg/kg Entelon150^® twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues. Results: The calcium content of the implanted tissue in the Entelon150^® group (0.013±0.004 mg/g) was lower than that in the control group (0.066±0.039 mg/g) (p=0.008). The losartan (0.024±0.016 mg/g, p=0.032) and rosuvastatin (0.022±0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150^® group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150^® group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150^® group compared with those in the control group. Conclusions: Entelon150^® exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.