• 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.

• Fashion & Textile Research Journal
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• v.7 no.3
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• pp.291-300
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• 2005

The purpose of this study is to investigate, analyze the purchasing behavior of fashion goods according to life style and role model of preteen generation, and provide manager or marketing planner for the reference data so that they can understand preteen generation and make proper strategy efficiently. So called, preteen market focusing on 1014 generation (from ten to fourteen years old) is highlighted. This generation created between the year 1989 to 1993 after Seoul Olympic monopolize parent's love in abundant economic environment and rise to the core of consumption subject. Products aiming at this preteen generation continuously though consumption mind was shrunk greatly due to recession. Only 2~3 years before preteen market was regarded as grey zone which doesn't belong to not only children (between six and nine years old) but also teenagers (between fifteen to eighteen years old). But in recent day their purchasing powers have increased rapidly and age group is divided on details, so that preteen market has become a niche market. Subjects were 333 persons consisting of students in the 4th~6th grade of primary school and the 1st~2nd grade of middle school in Daegu city. Measuring instruments are as follows: 5questions to differentiate preteen generation, 22 questions to measure life style, 17questions (which have six sub-factors such as purchase motive, factor of product selection, utilization of informant, purchase time, purchase place, and purchase method) to measure the purchase behavior of fashion goods measurement, and 16 questions (which have four sub-factors such as parent, entertainer & sports stars, brothers and sisters, friends) to measure model of role. Statistical data were processed by SPSS 10.0 programs. Frequencies, Factor analysis, Cluster analysis, ANOVA, Cross analysis, Multiplex regression analysis, and Duncan's multiple range test were carried out.

• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.339-347
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• 2007

SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

• Journal of health informatics and statistics
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• v.43 no.4
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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.

• Journal of Hospice and Palliative Care
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• v.13 no.1
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• pp.7-12
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• 2010

Purpose: To evaluate medications at the end of life care for terminal cancer patients during their last admission. Methods: Medical records of terminal cancer patients during their last admission from July 2003 to April 2008 at a district academic hospital were evaluated. Patient's characteristics, therapeutic drug classification during their last admission and on the patient's day of death, and the administrated route and number of medications on the patient's day of death were analyzed. Results: Total 81 patients were included. The median patient age was 63 years. The median length of admission was 18 days (range: 1~101). 54% of the patients had more than one comorbidities. The most frequently prescribed drugs during the last admission were opioid analgesics (63%), followed by antibiotics (58%) and antacids (53%). On the day of death, common medications were antibiotics (59%), antacids (58%), and opioid analgesics (46%). Intravenous injection was given to 81% of the patients and intramuscular injection was given to 16% of the patients on the day of patient's death. Number of medications prescribed to patients was between 0 and 11 (median: 3) and 12% (10/81) of the patients took over 8 medications including intravenous and oral drugs on the day of death. 6% (5/81) of the patients took potentially futile medications, like multivitamin or statin until the day of death. Conclusion: This study suggests that potentially futile medications and uncomfortable care were given to terminal cancer patients. Multicenter-based studies are necessary to diminish futile medications by essential medication at the end of life care for terminal cancer patients.

• Journal of Life Science
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• v.24 no.11
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• pp.1209-1216
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• 2014

The aim of this study was to investigate the effect of water-soluble sulfated ${\beta}$-glucan (SBG) obtained from Ganoderma lucidum mycelia on the antihyperlipidemic and serum lipid levels in high-fat diet-induced obese rats. Five-week-old male Sprague-Dawley rats were fed a high-fat diet for two weeks to induce obesity. They were ten divided into five groups-normal control diet group (NC), high-fat control diet group (HC), high-fat diet and 200 mg/kg of SBG group (HC-HSBG), high-fat diet and 20 mg/kg of SBG group (HC-LSBG), and high-fat diet and 20 mg/kg of lovastatin group (HC-Lov)-and fed one of five diets for two more weeks. Although food intake and final body weight after four weeks of SBG consumption were similar in the five experimental groups, food efficiency ratio was higher in the high-fat diet groups(2, 3, 4, and 5) than in the NC group. In evaluating the hematological parameters of the rats, the neutrophil and monocyte ratios were higher in the HC-HSBG, HC-LSBG, and HC-Lov groups than in the HC group. Serum lipid profiles were analyzed after a 12 hr fast at the end of the study. Total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower in the HC-HSBG and HC-LSBG groups than in the HC group. These results suggest that chemically engineered sulfated mushroom ${\beta}$-glucan (SBG) might contribute to lower cholesterol and lipid levels in blood.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.164-172
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• 2012

This study was aimed to increase the solubility, dissolution and permeation rates of atorvastatin calcium (ATC) using bile salt and/or 2-hydroxypropyl-${\beta}$-cyclodextrin ($HP{\beta}CD$). From solubility studies, sodium deoxycholate (SDC) among bile salts studied was found to have the highest solubilizing effect on ATC ($4.4{\pm}0.4$ mg/ml), and the order of increasing solubility was SDC>sod. cholate>sod. glycocholate>sod. taurodeoxycholate>sod. taurocholate>conjugated bile acid. ATC solid dispersions were prepared at various ratios of drug to SDC and/or $HP{\beta}CD$, and evaluated by differential scanning calorimetry (DSC), dissolution studies and dissolution-permeation studies. DSC curves showed amorphous state of ATC in the physical mixture and solid dispersion. Dissolution rates of ATC-SDC solid dispersions and physical mixture were markedly increased at pH 6.8, but decreased at pH 1.2 with greater proportions of SDC due to the precipitation of SDC, compared with that of drug alone. On the other hand, dissolution rates of ATC-$HP{\beta}CD$ solid dispersion and physical mixture at pH 1.2 were varied with the ratio of drug to carriers. From duodenal permeation studies, it was found that fluxes of ATC (donor dose: 0.5 mg/3.5 ml) in the presence of 25 mM sodium glycocholate, SDC, sod. cholate and sod. taurocholate $(5.7{\pm}0.9$, $5.6{\pm}0.9$, $4.8{\pm}0.7$ and $4.6{\pm}0.9\;{\mu}g/cm^2/hr$, respectively) were enhanced, compared with drug alone ($3.4{\pm}0.9\;{\mu}g/cm^2/hr$). In the dissolution-permeation studies, 1 : 9 : 10 (w/w) ATC-SDC-$HP{\beta}CD$ solid dispersion increased the flux 2.2 times, compared with 1 : 5 : 4 (w/w) ATC-lactose-corn starch mixture as control. In conclusion, solid dispersions with bile salt and $HP{\beta}CD$ were found to be an effective means for increasing the dissolution and permeation rates of ATC.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.