• 한국임상약학회지
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• 제28권4호
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• pp.293-299
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• 2018

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ${\leq}75$ with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40-75 with ${\geq}7.5%$ estimated 10-year ASCVD risk and LDL-C ${\geq}190mg/dL$. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. Methods: Adults (${\geq}18years$) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Center criteria were analyzed. Results: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to low-intensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG ($67{\pm}14$ vs $62{\pm}12$). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). Conclusion: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.

• 한국발생생물학회지:발생과생식
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• 제11권2호
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• pp.59-66
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• 2007

배아줄기세포를 이용한 치료법 개발을 위해서는 배아줄기세포의 자가재생산 및 분화과정을 조절하는 분자적 기전을 이해하는 것이 매우 중요하다. 지질합성경로(Mevalonate pathway)에 작용하는 HMG-CoA 환원효소(Hydroxymethylglutaryl-coenzyme A reductase)의 억제제인 스타틴은 콜레스테롤 저하제로 잘 알려져 있으며, 콜레스테롤 이외에 단백질 isoprenylation의 기질로 작용하는 아이소프레노이드(Isoprenoids)(Farnesyl pyrophosphate(FPP), Geranylgeranyl pyrophosphate(GGPP))의 생성을 억제하는 효능을 가지고 있다. 스타틴에 의해 매개되는 표적단백질의 isoprenylation 억제는 다양한 세포내 신호전달과정에 영향을 미치게 되며, 결과적으로 세포기능을 조절하는데 핵심적인 역할을 하게 된다. 스타틴이 첨가된 배양배지에서 배양된 배아줄기세포는 자가재생산능이 억제되고 분화가 촉진되는데, 특히 지방/골세포 직계열로의 분화가 촉진된다. 배아줄기세포에서의 스타틴의 효과 및 작용기전에 대한 이해가 아직은 미비한 수준이나, 최근 우리 연구팀에서는 스타틴이 콜레스테롤 작용과는 무관하게 RhoA G-단백질의 세포내 분포 및 활성을 억제함으로써 배아 줄기세포의 자가재생산능을 억제하고 있음을 규명하였다. 스타틴 다면효과와 그 작용에 대한 이해는 배아줄기세포의 미분화 및 분화상태를 조절하는데 관여하는 분자적 조절기전을 이해하는데 중요한 모델이 될 수 있을 것으로 추정된다.

• Archives of Plastic Surgery
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• 제36권5호
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• pp.525-530
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• 2009

Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.