• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.135-142
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• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.

• 대한한의학방제학회지
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• 제29권4호
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• pp.239-252
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• 2021

Objectives : This study is to effect of improving muscle atrophy through water extract on the solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis in an atorvastatin-induced atrophy C2C12 cell. Methods : C2C12 myoblast were differentiated into myotube by 2% horse serum medium for 6 days, and then treated solid-phase fermentation(S-P) extract at different concentrations for 24h. To investigate the effect of S-P extract on the induction of muscle atrophy and expression of atrophy-related genes and apoptosis in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : As a result of treatment with atorvastatin at concentrations of 5, 10, and 20 uM on the 6th day of differentiation in C2C12 myotube cells, it was confirmed that the cell morphology was damaged in a concentration-dependent manner, and the length and thickness of the myotube also decreased in a concentration-dependent manner. Treatment with S-P extract (50, 100 and 200 ㎍/㎖) increased of GSH and inhibited ROS in the atorvastatin-induced muscle atrophy cell model at a concentration that did not induce toxicity. In addition, it was confirmed that it has an effect on muscle reduction by inhibiting apoptosis of muscle cells as well as being involved in protein production and degradation of muscle cells. Conclusions : Atorvastatin-induced atrophy C2C12 cell, S-P extract activates related to differentiation/generation and proteolysis, and inhibits cell death of atrophy in C2C12 cell. Based on this, it is necessary to prove its effectiveness through animal models and human application test, but it is considered to be discarded Schisandra chinensis can present the potential for development as a recycling industrial material.

• 한국임상약학회지
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• 제30권2호
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• pp.73-80
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• 2020

Objective: The Australian Pharmaceutical Benefits Scheme (PBS) is a national drug subsidy program. Given the similarity and comprehensiveness of the Australian PBS and the Korean National Health Insurance (NHI) data, these data are increasingly used for pharmacoepidemiological investigations, as well as international comparative studies. This study aims to introduce the various sources of publicly available PBS data and provide a practical guide to researchers conducting drug utilization studies. Methods: We searched literature and websites to detail and compare the collection, structure, components, and characteristics of each PBS data format. We identified different characteristics of the PBS data from the Korean NHI claims data which are mainly owing to their unique co-payment policies and data collection processes. In addition, the utilization and expenditure of atorvastatin, a widely used treatment for hyperlipidemia, were analyzed using two different sources of PBS data and the different results were interpreted. Results: There exist differences in when data were collected or non-subsidized uses of medicine were included among sources of PBS data. Additionally, two countries have different cost sharing methods inmedicine subsidy scheme; co-payment in Australia and co-insurance in Korea. Therefore, it should be noted that prescriptions under co-payment are not included in some data sources in Australia. Conclusion: Despite several analytical challenges, open access and easy data management are the strengths of the PBS data sources. A detailed knowledge of the PBS data can ensure robust methodology and interpretation of pharmacoepidemiological investigations or international comparative studies.

• 대한한방내과학회지
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• 제38권5호
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• pp.548-554
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• 2017

Objective: A general prejudice exists that all herbal medicines are not good for liver. We report that herbal medicine can have positive effects on the liver, based on the improved liver function test levels observed in one patient. We also suggest the effectiveness of co-administration of herbal and western medicines. Methods: We checked the liver function test levels of one patient measured on 12 July at another hospital. We identified worse levels on 7 August, when he was first admitted to Semyung University Hospital. We measured liver function test levels of the same patient after treatment with Korean herbal medicine on 14 and 21 August during hospitalization at Semyung Hospital. We compared the figures and evaluated the effectiveness of 'Saenggangeonbi-tang' herbal medicine in the liver. Results: The patient's liver function test levels were normal on 12 July, but had become abnormal by 7 August, when he was admitted to Semyung Hospital. The cause of liver dysfunction was suggested as Atorvastatin, one of the western drugs he had started to take. Continuous treatment with Korean herbal medicine resulted in a definite improvement in liver function. Conclusion: Korean herbal medicine can provide positive improvements in liver function test levels.

• Journal of health informatics and statistics
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• 제43권4호
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• pp.329-335
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• 2018

Objectives: In recent years, there has been an increased need for a way to extract desired information from multiple medical literatures at once. This study was conducted to confirm the usefulness of unstructured data analysis using previously published medical literatures to search for new indications. Methods: The new indications were searched through text mining, network analysis, and topic modeling analysis using 5,057 articles of atorvastatin, a treatment for hyperlipidemia, from 1990 to 2017. Results: The extracted keywords was 273. In the frequency of text mining and network analysis, the existing indications of atorvastatin were extracted in top level. The novel indications by Term Frequency-Inverse Document Frequency (TF-IDF) were atrial fibrillation, heart failure, breast cancer, rheumatoid arthritis, combined hyperlipidemia, arrhythmias, multiple sclerosis, non-alcoholic fatty liver disease, contrast-induced acute kidney injury and prostate cancer. Conclusions: Unstructured data analysis for discovering new indications from massive medical literature is expected to be used in drug repositioning industries.

• 대한한의학방제학회지
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• 제22권1호
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• pp.167-176
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• 2014

Objectives : This study investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF, and DF+GSH groups given a high fat diet with atorvastatin (10 mg/kg), DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Circulating concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol were decreased in DF, DF+GSH and atorvastatin groups compared with control. The decreases were significant in DF+GSH and atorvastatin groups. 3. Liver weights were decreased in DF, DF+GSH and atorvastatin groups compared with control. In particular, liver weight was significantly reduced only in DF+GSH group. 4. Hepatic lipid accumulation was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control, and the magnitude of which was more effective in DF+GSH group than in DF-only group. 5. Circulating ALT concentrations were decreased in DF, DF+GSH and atorvastatin compared with control, but ALS levels were significantly reduced only in DF+GSH group. Conclusions : In conclusion, these results suggest that DF decreases body weight gain, improves blood lipid metabolism, and reduces liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• 대한한의학방제학회지
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• 제22권1호
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• pp.113-122
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• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF-a, and DF-b groups given a high fat diet with atorvastatin (10 mg/kg), DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The extent of decreases was eminent in DF-a group. 2. Circulating concentrations of total cholesterol and LDL-cholesterol were significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The decreases were most effective in atorvastatin group. 3. Liver weights were decreased in DF-a, DF-b, and atorvastatin groups compared with control. In particular, liver weight was significantly reduced in DF-b group. 4. Hepatic lipid accumulation was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control, and the magnitude of which was most effective in DF-b group. 5. Circulating ALT concentrations were decreased in DF-a, DF-b, and atorvastatin groups compared with control, but ALS levels were significantly reduced only in DF-b group. Conclusions : In conclusion, these results suggest that DF-a and DF-b decrease body weight gain, improve blood lipid metabolism, and reduce liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were similar between Pakistani and Chinese Ephedra herba-containing Gangjihwan.

• Parasites, Hosts and Diseases
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• 제56권2호
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• pp.105-112
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• 2018

Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA were apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with highreduction in Blastocystis shedding (93.4-97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%)were recorded in groups of combination treatments AVA 20-40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.

• Mycobiology
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• 제41권2호
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• pp.94-99
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• 2013

In this study, ethanolic extracts from Hericium erinaceum cultivated with Artemisia capillaris (HEAC) were assessed for their ability to lower the cholesterol levels of male Sprague-Dawley rats fed a high-fat diet. Rats were randomly subdivided into seven test groups. Each group contained eight rats fed a high-fat diet during a growth period lasting 4 wk. Supplementation with the extracts was performed once a day for 2 wk after the high-fat diet. The control group (rats fed a high-fat diet) showed a high efficiency ratio (feed efficiency ratio) value compared to the normal group. Biochemical parameters, including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels dramatically increased in the control group compared to the normal group. High-density lipoprotein-cholesterol (HDL-c) content in the control group was also significantly lower relative to the normal group. Two positive control groups, treated with simvastatin and atorvastatin, had lowered TC, LDL-c, and TG levels, and increased HDL-c content compared to the control group. Treatment with the tested extracts, including HEAC, ethanolic extracts from Hericium erinaceum, and ethanolic extracts from Artemisia capillaris reduced TC, LDL-c, and TG levels and elevated HDL-c content in the hyperlipidemia rats. The atherogenic index and cardiac risk factor values for the HEAC-treated group were 0.95 and 1.95, respectively. Simvastatin- and atorvastatin-treated groups showed atherogenic index values of 1.56 and 1.69, respectively, and cardiac risk factor values of 2.56 and 2.69, respectively. These results show HEAC possesses an ability to cure hyperlipidemia in rats and may serve as an effective natural medicine for treating hyperlipidemia in humans.

• BMB Reports
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• 제54권3호
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• pp.170-175
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• 2021

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.