• Health Policy and Management
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• v.9 no.3
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• pp.70-94
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• 1999

This paper was performed for a cost-effectiveness analysis of pharmacologic treatment of hypercholesterolemia. Agents modeled were cholestyramine, gemfibrozil. bezafibrate, lovastatin, pravastatin, simvastatin. Pharmacologic effectiveness was estimated by regression from reported clinical trials. Pharmacologic effects were expressed as the percent change of blood cholesterol level. Cost estimates included patients' travel expenses and time loss as well as resource consumption in the health care sector. Bezafibrate was the most efficient agent for reducing total cholesterol levels, having an cost over 1 year of ￦31.400 per percent reduction in total cholesterol. Simvastatin (10mg/d) was also efficient(￦33,100 per percent reduction). Chole styramine(8g/d) was least efficient at ￦90,200. For low-density lipoprotein cholesterol. simvastatin(10mg/d) was most efficient, at ￦23,200 per percent reduction, followed by lovastatin(20mg/d) at ￦28,000. Gemfibrozil was least efficient at ￦77,800 per percent reduction. For high-density lipoprotein cholesterol. bezafibrate(400mg/d) was most efficient at ￦39,300 per percent increase of high-density lipoprotein cholesterol. Cholestyramine was least efficient at ￦514,700. Analyses combining low-density lipoprotein cholesterol and high-density cholesterol effects suggest that bezafibrate(600mg/d) and simvastatin (10mg/d) were most efficient for reducing cardiovascular risk. The cost-effectiveness analysis results show that both simvastatin and bezafibrate could be efficient treatment. Simvastatin provide more effective treatment at higher cost, whereas bezafibrate is more cost-effective, as it may be less effective, at lower cost. Therefore, clinicians should choose reasonable treatment according to the patient's needs This pharmacoeconimc analysis will provide a guideline for efficient pharmacologic treatment and also be reference data for pricing new drugs.

• Nutrition Research and Practice
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• v.2 no.4
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• pp.211-217
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• 2008

This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p<0.01), and the elevated plasma total cholesterol of SIM group was significantly decreased in SIM-onion and SIM-beet groups (p<0.05). HDL-cholesterol in SIM-beet group was significantly increased compared with other groups (p<0.05). Platelet aggregation in both the maximum and initial slope was significantly decreased in SIM group compared with SIM-onion group (p<0.05). Na-K ATPase was significantly decreased in SIM group compared with the control, SIM-onion and SIM-beet groups (p<0.05). Na passive leak was significantly increased in all groups treated with SIM compared with the control (p<0.05). The total Na efflux was decreased in SIM group and increased in SIM-onion group and the difference between these two groups was significant (p<0.05). There was no difference in intracellular Na among groups. In present study, simvastatin, a HMG CoA reductase inhibitor at dose of 2mg/kg BW/day rather increased plasma total cholesterol in rats, inferring that the action mechanism of simvastatin on cholesterol metabolism differ between rat and human. Onion and beet play favorable roles in cardiovascular system by restoring the reduced Na efflux through Na-K ATPase and Na-K cotransport in SIM treated rats.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.172-179
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• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.281.1-281.1
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• 2003

Purpose. The purpose of this study was to develop and validate sensitive and specific analytical method for determinination of simvastatin in human plasma by the column-switching high-performance liquid chromatography (HPLC) system with UV detection. Methods. Simvastatin and internal standard were extracted into diethyl ether from plasma. (omitted)

• Journal of Korean Neurosurgical Society
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• v.58 no.4
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• pp.328-333
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• 2015

Objective : The goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients. Methods : This study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis. Results : Ninety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups. Conclusion : This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.121-127
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• 2003

The objective of this study was to solidify the simvastatin self-microemulsifying drug delivery system (SMEDDS) and to improve the encapsulation efficiency of solidified alginate beads using sodium alginate. Typical simvastatin SMEDDS was composed of various oils, surfactants and cosurfactants. Also solidified-alginate beads was prepared by crosslinking liquid emulsion mixtures containing sodium alginate and other excipients (cetylpyridinum chloride (CP-Cl), hydroxypropyl methylcellulose, starch and so on). in $CaCl_2$ solution, it has been investigated that the drug release pattern and encapsulation efficiency were varied with the ratio of cationic lipid (CP-Cl). Solidified sodium alginate beads containing simvastatin SMEDDS were redispersed into media without re-aggregation. Oil droplet size of redispersed solidified-beads in media produced smaller than the initial size. The density of beads and drug loading amount were increased with increasing cationic lipid content. These systems have advantages of storage stability and predictability of drug release rate.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• Imaging Science in Dentistry
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• v.38 no.3
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• pp.133-146
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• 2008

Purpose : To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. Materials and Methods : 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. Conclusion : As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

• 대한임상약리학회:학술대회논문집
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• 2006.11a
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• pp.75-75
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• 2006

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.162-163
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• 2001