• 생물정신의학
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• 제13권3호
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• pp.152-161
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• 2006

Objective : The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type : Glu, 'H' ; variant : Lys, 'h') and Glu308Gly(wild-type : Glu, 'D' ; variant : Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. Methods : Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. Results : A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. Conclusion : The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.9-18
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• 1993

Sugar spheres loaded with melatonin (MT) were coated with $Aquacoat^{\circledR}$ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with $Aquacoat^{\circledR}$ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 mg MT as low dose (immediate release portion of MT, 0.1 mg) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/ml and maintained at about 10 pg/ml over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 mg MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.

• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.287-293
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, Amaryl tablet (Handok & Aventis Korea, reference drug) and Mepiril tablet (Myungmoon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (glibenclamide) to human plasma, plasma samples were extracted using 1mL of methyl tertiary butyl ether. Compounds extracted were analyzed by reverse-phase HPLC with multiple reaction monitoring (MRM) mode analyte detection. This method for determination glimepiride proved accurate and reproducible, with a limit of quantitation of 2 ng/mL in human plasma. Twenty-four healthy male Korean volunteers received each medicine at the glimepiride dose of 2 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of glimepiride were monitored by a LC-MS/MS for over a period of 12 hr after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from 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 Amaryl/Mepiril were log 0.9583-log 1.1357 and log 1.0570-log 1.2376, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Taken together, our study demonstrated the bioequivalence of Amaryl and Mepiril with respect to the rate and extent of absorption.

• Journal of Microbiology and Biotechnology
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• 제27권2호
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• pp.388-394
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• 2017

Although several analytical methods for measuring total antioxidant capacity (TAC) have been applied to biological samples, there were often dissimilar results due to the different principles of methods applied. Thus, this study aimed to validate four conventional analytical methods for measuring plasma TAC, including the ABTS assay, DPPH assay, FRAP assay, and ORAC assay, by comparing with urinary 8-isoprostane concentration. In addition, TAC results were compared with antioxidant enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase in erythrocyte, and catalase in plasma. Plasma TAC measure by ABTS assay was strongly correlated with the result by FRAP assay. Plasma TAC by FRAP and ORAC assays were negatively correlated with erythrocyte SOD activity. The agreement among the four TAC assay methods and 8-isoprostane was determined using 95% prediction limits of linear regression, expressed as the mean of 8-isoprostane ${\pm}95%$ prediction limits. The ABTS method better agreed with 8-isoprostane than the other methods, demonstrating narrow prediction of limits. Furthermore, only plasma TAC determined by the ABTS assay was inversely correlated with urinary 8-isoprostane (r = -0.35, p < 0.05). In summary, the ABTS assay would be an appropriate method to measure overall plasma antioxidant capacity and predict the body's antioxidant status.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.554-558
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• 1996

High-performance liquid chromatographic method was developed for the determination or LB 20304 (compound 1) in the plasma of rats and dogs. The analyte was deproteinized with 1 volume of methanol and 1/2 volume of 10% zinc sulfate, and the supernatant was injected onto a reversed-phase HPLC column. The mobile phase was a mixture of 24 parts of acetonitrile and 76 parts of 0.1% trifluoroacetic acid. The flow rate was 1 ml/min, and the effluent was monitored by fluorescence detector at an excitation wavelength of 337 nm and an emission wavelength of 460 nm. The retention time of compound 1 was 6.3 min. The assay of compound 1 was linear over the concentration range of 0.2-100.mu.g/ml in the plasma of rats and dogs. The lower limit of quantification was 0.2.mu.g/ml using 100.mu.l of plasma with a 97-99% accuracy and a 12-14% precision. In the 0.5, 5, and 50.mu.g/ml quality control samples, the intra- and inter-day accuracy were 88-95% and 88-97%, whereas intra- and interday precision were 0.5-6.6% and 0.2-9.3%, respectively, in the plasma of rats and dogs. The recoveries were 68-71% independent of concentration and species in the plasma. No interferences from endogenous substances were observed. Taken together, the above HPLC assay method by deproteinization and fluorescence detection was suitable for the determination of compound 1 in the preclinical pharmacokinetics.

• Transactions on Electrical and Electronic Materials
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• 제10권2호
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• pp.53-57
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• 2009

In this paper we develop a method to observe faults in semiconductor devices and transmission lines by calculating the variation of the reflection function in a dielectric microstrip line that has an open-ended termination containing an optically induced plasma region. It is analyzed with the assumption that the plasma is distributed homogeneously in laser illumination. With the non linear material of degradation, the concentration of the carrier in the part of the material has changed. Since the input wave has produced the phenomenon of reflection, the input signal to the open-ended microstrip lines can be observed on reflection to identify the location of the fault. The characteristic impedances resulting from the presence of plasma are evaluated by the transmission line model. The variation of the reflection wave in the microwave system has been calculated by using an equivalent circuit model. The transient response has been also evaluated theoretically for changing the phase of the variation in the reflection. The variation of characteristic response in differentially localized has been also evaluated analytically.

• 한국전기전자재료학회논문지
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• 제20권1호
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• pp.1-7
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• 2007

In this paper, two kinds of initial oxidation methods i.e., SLTO(Slow Low Temperature Oxidation: $700^{\circ}C$) and RTO(Rapid Thermal Oxidation: $850^{\circ}C$) are applied prior to the plasma nitridation for ultra thin oxide of RPNO (Remote Plasma Nitrided Oxide). It is observed that SLTO has superior characteristics to RTO such as lower SS(Sub-threshold Slope) and improved Ion-Ioff characteristics. Low frequency noise characteristics of SLTO also showed better than RTO both in linear and saturation regime. It is shown that flicker noise is dominated by carrier number fluctuation in the channel region. Therefore, SLTO is promising for nano-scale CMOS technology with ultra thin gate oxide.

• 제어로봇시스템학회논문지
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• 제4권4호
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• pp.506-516
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• 1998

In this paper, an algorithm is proposed to detect the malfunction of plasma-etching characteristics using EPD signal trajectories. EPD signal trajectories offer many information on plasma-etching process state, so they must be considered as the most important data sets to predict the wafer states in plasma-etching process. A recent work has shown that EPD signal trajectories were successfully incorporated into process modeling through critical parameter extraction, but this method consumes much effort and time. So Principal component analysis(PCA) can be applied. PCA is the linear transformation algorithm which converts correlated high-dimensional data sets to uncorrelated low-dimensional data sets. Based on this reason neural network model can improve its performance and convergence speed when it uses the features which are extracted from raw EPD signals by PCA. Wafer-state variables, Critical Dimension(CD) and uniformity can be estimated by simulation using neural network model into which EPD signals are incorporated. After CD and uniformity values are predicted, proposed algorithm determines whether malfunction values are produced or not. If malfunction values arise, the etching process is stopped immediately. As a result, through simulation, we can keep the abnormal state of etching process from propagating into the next run. All the procedures of this algorithm can be performed on-line, i.e. wafer to wafer.

• Journal of Information Display
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• 제8권3호
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• pp.5-10
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• 2007

Twin target sputtering (TTS) system with a configuration of vertically parallel facing Al targets and a substrate holder perpendicular to the Al target plane has been designed to realize a direct Al cathode sputtering on organic light emitting diodes (OLEDs). The TTS system has a linear twin target gun with ladder type magnet array for effective and uniform confinement of high density plasma. It is shown that OLEDs with Al cathode deposited by the TTS show a relatvely lower leakage current density $({\sim}1{\times}10^{-5}mA/cm^2)$ at reverse bias of -6V, compared to that ($1{\times}10^{-2}{\sim}10^{-3}$ $mA/cm^2$ at -6V) of OLEDs with Al cathodes grown by conventional DC magnetron sputtering. In addition, it was found that Al cathode films prepared by TTS were amorphous structure with nanocrystallines due to low substrate temperature. This demonstrates that there is no plasma damage caused by the bombardment of energetic particles. This indicates that the TTS system with ladder type magnet array could be useful plasma damage free deposition technique for direct Al cathode sputtering on OLEDs or flexible OLEDs.

• Journal of Pharmaceutical Investigation
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• 제30권4호
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• pp.279-282
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• 2000

Simple and precise high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of a HMG-CoA reductase inhibitor, $lovastatin^{TM}$ and its active metabolite (mevinolinic acid) in human plasma. The method involved solid phase extraction of mevinolinic acid and internal standard using Sep-Pak Cartridge. Samples were analyzed by reversed-phase HPLC using $Capcell-Pak\;C_{18}$ column with ultraviolet detection at 238 nm. The quantitation limit of mevinolinic acid was 2 ng/ml and the calibration curve was linear over the range of 2-50 ng/ml $(r^2>0.999)$ with human plasma. The analyses of quality control samples indicated that the normal values could be predicted with an accuracy >97%. The intra- and inter-day coefficients of variation for the analyses were <10%. The average recoveries were similar (79%) for mevinolinic acid and methylmevinolinic acid. The method described has been successfully applied to the quantification of mevinolinic acid in about 1,000 human plasma samples over six-month period.