• Korean Journal of Clinical Pharmacy
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• v.24 no.4
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• pp.231-239
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• 2014

Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.111-117
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• 2008

To overcome the solubility of poorly water-soluble drug, the formation of solid dispersion using a spray-dryer with polymeric material, that can potentially enhance the dissolution rate extend of drug absorption was considered in this study. $Eudragit^{(R)}$ E100 as carrier for solid dispersion is acrylate copolymer that soluble in acidic buffer solutions (below pH 5.0). It was used to increase dissolution of atorvastatin calcium as a water-insoluble drug in acidic environments. In this study, a spray-dryer was used to prepare solid dispersion of atorvastatin calcium and $Eudragit^{(R)}$ E100 for purpose of improving the solubility of drug. Atorvastatin calcium and $Eudragit^{(R)}$ E100 were dissolved in ethanol and spray-dryed. DSC and XRD were used to analyze the crystallinity of the sample. It was found that atorvastatin calcium is amorphous in the $Eudragit^{(R)}$ E100 solid dispersion. FT-IR was used to analyze the salt formation by interaction between atorvastatin calcium and $Eudragit^{(R)}$ E100. Comparative dissolution study exhibited better dissolution characteristics than the commercial drug ($Lipitor^{(R)}$) as control. The dissolution rate of atorvastatin calcium was markedly increased in solid dispersion system in simulated gastric juice (pH 1.2). This study proposed that this solid dispersion system improved the bioavailability of poorly water-soluble atorvastatin calcium.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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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 $Tablet^{(R)}$.

• Analytical Science and Technology
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• v.22 no.5
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• pp.407-414
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• 2009

A simultaneous determination method for cholesterol, lanosterol and desmosterol was developed using gas chromatography/mass spectrometry. Urine was enzymatically hydrolyzed with ${\beta}$-glucuronidase/arylsulfatase. Samples were prepared using extractions with a mixture of ethyl acetate-hexane (2:3, v/v), followed by derivatization with a mixture of MSTFA/TMSI/TMCS (100:2:5 v/v/v). All analyses were performed using GC/MS in selective ion monitoring mode. Good linearities ($r^2=0.998{\sim}0.999$) in calibration curve and a satisfactory recovery (80.0%~113%) were achieved. Accuracy and precision values within ${\pm}15%$ in the concentration range of 5 to 200 ng/mL were also observed for all compounds. The developed method was applied to pravastatin-treated (70 and 250 mg/kg/day for 7 days, oral) hyperlipidemia rats. Those sterols were significantly lower in drug-treated rats compared to the controls, which justifies the drug efficacy. Therefore, these results indicate that the developed method was successfully applied to examine statin drug efficacy with urine sample.

• Journal of Life Science
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• v.33 no.12
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• pp.967-977
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• 2023

Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.

• Journal of Medicine and Life Science
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• v.21 no.2
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• pp.40-48
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• 2024

Understanding the effectiveness of statin treatment is essential for developing tailored stroke prevention strategies. We aimed to evaluate the efficacy of statin treatment in preventing recurrent stroke among patients with various ischemic stroke subtypes. Using data from the Clinical Research Collaboration for Stroke-Korea-National Institute for Health (CRCS-K-NIH) registry, we included patients with acute ischemic stroke admitted between January 2011 and July 2020. To evaluate the differential effects of statin treatment based on the ischemic stroke subtype, we analyzed patients with large artery atherosclerosis (LAA), cardio-embolism (CE), and small vessel occlusion (SVO). The primary outcomes were recurrent ischemic stroke and recurrent stroke events. The hazard ratio for outcomes between statin users and nonusers was compared using a Cox proportional hazards model adjusted for covariates. A total of 46,630 patients who met the inclusion criteria were analyzed. Statins were prescribed to 92%, 93%, and 78% of patients with LAA, SVO, and CE subtypes, respectively. The hazards of recurrent ischemic stroke and recurrent stroke in statin users were reduced to 0.79 (95% confidence interval [CI], 0.63-0.99) and 0.77 (95% CI, 0.62-0.95) in the LAA subtype and 0.63 (95% CI, 0.52-0.76) and 0.63 (95% CI, 0.53-0.75) in CE subtype compared to nonusers. However, the hazards of these outcomes did not significantly decrease in the SVO subtype. The effectiveness of statin treatment in reducing the risk of recurrent stroke in patients with LAA and CE subtypes has been suggested. Nonetheless, no significant effect was observed in the SVO subtype, suggesting a differential effect of statins on different stroke subtypes.

• Journal of Life Science
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• v.21 no.8
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• pp.1149-1155
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• 2011

Myostatin (MSTN) belongs to the transforming growth factor-${\beta}$ superfamily or growth and differentiation factor 8 (GDF-8), and functions as a negative regulator of skeletal muscle development and growth. Previous studies in mammals have suggested that myostatin knock-out increased muscle mass and decreased fat content compared to those of the wide type. Recently, several studies on myostatin have beenconducted on the block myostatin signal pathway with myostatin antagonists and the MSTN regulation with RNAi to control myostatin function. This study was performed to analyze growth and muscle alteration of Oncorhychus masou by treatment with recombinant myostatin prodomains derived from fish. We designed myostatin prodomains derived from P. olivaceus (pMALc2x-poMSTNpro) and S. schlegeli (pMALc2x-sMSTNpro) in a pMALc2x expression vector, and then purified the recombinant proteins using affinity chromatography. The purified recombinant proteins were treated in O. masou through an immersion method. Recombinant protein treated groups did not show a significant difference in weight, protein, or lipid composition compared to the control. However, there was a difference in the average number and area for histological analyses in the muscle fiber. At twelve and twenty-two weeks from the initial treatment, there were differences in averagefiber number and area between the 0.05 mg/l treated-group and the control, but the numbers were similar to those of the control during the same time period. At twelve weeks, however, 0.2 mg/l treated-group had an increase in average fiber number and decrease in average fiber area compared to the control. At twenty-two weeks, the pMALc2x-sMSTNpro 0.2 mg/l treated-group was induced and showed a decrease in average fiber number and increase in average fiber area. The results between twelve and twenty-two weeks showed that the fiber numbers had decreased, whereas average fiberarea had increased due to sMSTNpro. It is understood that the sMSTNpro induced only hyperplasia at twelve weeks, after which it induced hypertrophy. Recombinant myostatin prodomains derived from fish may induce hyperplasia and hypertrophy in O. masou depending upon the time that has elapsed.