• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.31-35
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• 2020

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.624-627
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• 2004

A bile acid derivative, methyl chalate （1）, was isolated from EtOAc extract of the fungus Rhizopus oryzae as a cholesterol biosynthesis inhibitor. It showed moderate inhibitory activity on cholesterol biosynthesis in human Chang liver cells. Compound 1 exhibited inhibitory effect on the later step of cholesterol biosynthesis, indicating that its action mode is different from that of statins that act on the HMG-CoA reductase.

• Journal of Korean Neurosurgical Society
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• v.50 no.5
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• pp.403-408
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• 2011

Objective : Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) $in$ $vivo$ suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH. Methods : Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured. Results : Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy. Conclusion : The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.

• Korean Journal of Clinical Pharmacy
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• v.31 no.4
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• pp.278-284
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• 2021

Background: Osteoporosis is a disease that affects the quality of life and imposes a high socioeconomic burden. Studies have reported that statins, a HMG CoA reductase inhibitor, have a positive or negative effect on osteoporosis. The purpose of this study was to analyze the correlation between statins and osteoporosis risk. Methods: We used the total patient sample data of the Health Insurance Review and Assessment Service (HIRA-NPS-2018). We analyzed the prevalence of osteoporosis in adult patients of Korea who were diagnosed with dyslipidemia and were prescribed statins at the same time. The odds ratio (OR) according to the intensity and type of statin was used to confirming the prevalence. Results: Among the 1,138,899 patients included in the study, 143,895 patients used statins and 27,524 patients (19.13%) were diagnosed with osteoporosis in the statin group. The OR value of statin group was 0.96 (95% CI 0.94-0.98), confirming that the prevalence of osteoporosis decreased, and a significant decrease was seen in all statin intensity. Some of the moderate-intensity statins rather increased the prevalence of osteoporosis, but atorvastatin and rosuvastatin obtained positive results at both medium- and high-intensity doses, and lovastatin, a low-intensity statin, showed the greatest reduction in the prevalence of osteoporosis. Conclusion: We found that the prevalence of osteoporosis was reduced in the statin group, and there was a constant correlation regardless of gender or age. However, a large, prospective, double-blind and randomized study is needed for a long period of time to demonstrate the effectiveness of statins.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.86-91
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• 2006

There are 3 different hypotheses on how statins may affect bones, through promoting bone formation, inhibiting bone resorption or through anti-inflammatory effect. In the 3 cross-sectional studies above, one showed increase BMD at hip and spine, one showed increase BMD only at mid-forearm and one showed that the risk reduction in fractures is not explained by the changes in BMD however, all 3 studies showed a decrease in risk of fracture associated with statins. In the 2 prospective cohort studies, one showed the use of statins was not associated with BMD at any skeletal site or decreasing the risk of fracture, and the other showed statins except pravastatin decreased in risk of vertebrate fracture but not affecting lumbar spine BMD. All of case-control studies indicated reduction in fracture risk but did not provide any data regarding BMD. 2 of the randomized, controlled studies showed no significant reduction in fracture risk as well as statins' effects on BMD. Finally, one longitudinal study showed statin use reduced fracture risk and increased BMD. Among the conflicting results shown above, even when statin use was shown to increase BMD, it does not seem to account for the reduction in fracture risk. There may be different ways that statins affect bone other than those hypotheses proposed above. Many studies seem to agree that pravastatin does not have any effect on bone. Some studies suggested that the reason statins did not achieve clinically significant increases in BMD in some studies, is due to the low affinity of statins on bone; statins are designed to act in the liver therefore their effective concentration in extrahepatic tissue is low. The limitations to those studies discussed above. Many studies did not account for the change of lifestyle while subjects' were on statins. Increases in weight bearing exercise and changes in diet might affect BMD and thus reduce risk of fractures. Mental alertness and vision acuity might prevent falls from occurring; many statin-users in the studies were young so the risk of fractures from falls would be decreased. Almost all of the studies failed exclude patients with neurological problems. During study periods, many subjects may have been started on drugs for diseases that usually occur with aging which could cause drowsiness and lead to falls. The sample sizes used in some of the trials were small and the duration of treatment and follow up might not have been long enough to see clinically relevant results.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.24-31
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• 2013

Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.