• Title/Summary/Keyword: $C_{}$ max/

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Rapid and Simple Method for the Determination of Pregabalin in Human Plasma using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS): Application to a Bioequivalence Study of Daewoong Pregabalin Capsule To Lyrica® Capsule (Pregabalin 150 mg)

  • Jang, Ki-Ho;Seo, Ji-Hyung;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.41 no.4
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    • pp.255-262
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    • 2011
  • Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

Effects of Verapamil in Cardioplegic Perfusates on the Ischemic Myocardium in Isolated Rat Heart (흰쥐의 적출된 심장에서 Verapamil이 허혈성 심근에 미치는 효과)

  • Kim, Su-Cheol;Jo, Gyu-Seok;Park, Ju-Cheol;Yu, Se-Yeong
    • Journal of Chest Surgery
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    • v.30 no.2
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    • pp.119-124
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    • 1997
  • Using isolated rat heart preparations, we observed the protective effe ts of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at $25^{\circ}C$ Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by $25^{\circ}C$ cardioplegic solution (St. Thomas'Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group (n=12) and cold cardioplegic solution with verapamil (1 mg/L) in experimental group (n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure (LVP), + dp/dt max, coronary flow and creatine phosphokinase (CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dpldt max, coronary flow and CPK than control group (p < 0.05).

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Effects of ${Co_3}{O_4}$, and ${La_2}{O_3}$on the Magnetic Properties of Sr-Ferrite (${Co_3}{O_4}$${La_2}{O_3}$ 첨가가 Sr 페라이트의 자기적 특성에 미치는 영향)

  • Jang, Se-Dong;Kim, Chong-O;Kim, Jong-Hui
    • Korean Journal of Materials Research
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    • v.11 no.8
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    • pp.685-689
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    • 2001
  • We carried out these experiments to examine the effects of element substitution of Co and La-Co for Sr-ferrite. The calcined properties of Co and La-Co element substitution were examined, and also the sintered magnetic properties were measured with the stoichiometric condition. The magnetic properties of $(La-Co)_{0.3}-SrM$ composition are as follows; $(M_s)$: 71.08 emu/g, $iH_c$: 4.38 kOe and $B_r$ : 4.18 kG, $iH_ c$ :4.35 kOe, $BH_{max}$: 4.3 MGOe. The $BH_{max}$ value was increased up to 10 % compared with conventional values. Our results imply that the magnetic properties of Sr-ferrite can be improved by the substitution of those elements.

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Dust Explosion Characteristics of Multi-Walled Carbon Nano Tube (다중벽 탄소나노튜브의 분진폭발 특성)

  • Han, In Soo;Lee, Keun Won;Choi, Yi Rac
    • Korean Chemical Engineering Research
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    • v.55 no.1
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    • pp.40-47
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    • 2017
  • Dust explosion hazards are always present when combustible dusts are manufactured or handled in the process. However, industries is experiencing difficulty in establishing chemical accident prevention measures because of insufficiency of information on dust explosion characteristics of combustible dust handled in industry. In this study, we investigated experimentally dust explosion characteristics of two kinds of multi-walled carbon nano tubes (MWCNT) different in particle size distribution and examined classification of dust explosion hazardous area for MWCNT manufacturing or handling process by applying the NFPA 499 code. As a result, $P_{max}$, $K_{st}$, LEL, MIE and MIT of MWCNT 1 having $124.2{\mu}m$ median diameter are obtained 6.3 bar, $56bar{\cdot}m/s$, $125g/m^3$, over 1000 mJ, and over $650^{\circ}C$. $P_{max}$, $K_{st}$, LEL, MIE and MIT of MWCNT 2 having $293.5{\mu}m$ median diameter are 6.2 bar, $42bar{\cdot}m/s$, $100g/m^3$, over 1000 mJ, and over $650^{\circ}C$, respectively. MWCNT 1, 2 are not categorized as combustible dust listed in the NFPA 499 Code for classification of dust explosion hazardous area because explosion severity and ignition sensitivity of MWCNT 1, 2 are below 0.35 and 0.01, respectively.

Bioequivalence of Two Clarithromycin Tablets (클래리스로마애신 정제의 생물학적 동등성 평가)

  • 김종국;이사원;최하곤;고종호;이미경;김인숙
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.219-224
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    • 1998
  • The bioequivalence of two clarithromvcin products was evaluated with 16 normal male volunteers (age 23-28 yr, body weight 57.5-75.517g) following single oral dose. Test product was ReYon Clarithromycin tablets (ReYon Pharm. Corp., Korea) and reference product was Klarici $d_{R}$ tablets (Abbott Korea). Both products contain 250 mg of clarithromucin. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of clarithromycin was accomplished using a modified agar well diffusion bioassay. As a result of the assay validation, the quantification of clarithromycin in human serum by this technique was possible down to 0.03$\mu$g/ml using 100$\mu$l of serum. The coefficient of variation (C.V.) was less than 10%. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products P>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{24hr}$ (8.10$\pm$ 1.26 vs 8.22$\pm$ 1.627g . hr/ml), AUC from time zero to infinite (AU $Co_{\infty}$) (8.61 $\pm$ 1.28 vs 8.84$\pm$ 1.71 $\mu$g . hr/ml), maximum plasma concentration ( $C_{msx}$) (0.87$\pm$0.22 vs 0.88$\pm$0.19 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.69 $\pm$0.48 vs 2.56$\pm$ 0.51 hr). The differences of mean AU $Co_{24h}$, $C_{msx}$ and $T_{msx}$ between the two products (1.44, 1.39, and 4.65%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectivly. Although the power for $T_{max}$ was under 0.8, $T_{max}$. of the two products was not significantly different each other (p>0.05). These results suggest that the bioavailability of ReYon Clarithromycin tablets is not significantly different from that of Klarici $d_{R}$ tablets. Therefore, two products are bioequivalent based on the current results. results.sults.sults.s.s.s.s.s.s.s.

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Measurement of Phosphorus Buffering Power in Various Soils using Desorption Isotherm (탈착 등온식을 이용한 토양 중 인산 완충력 측정)

  • Lee, Jin-Ho;Doolittle, James J.
    • Korean Journal of Soil Science and Fertilizer
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    • v.37 no.4
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    • pp.220-227
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    • 2004
  • Phosphorus desorption study is essential to understanding P behavior in agricultural and environmental soils because phosphorus is considered as two different aspects, a plant nutrient versus an environmental contaminant. This study was conducted to determine soil P buffering power related to P desorption quantity intensity (Q/I) parameters, $Q_{max}$(an index of P release capacity) and $l_0$(an index of the intensity factor), and to investigate the characteristics of relationship between the P desorption Q/I parameters and the soil properties. Soil samples were prepared with treatments of 0 and $100mg\;P\;kg^{-1}$ applied as $KH_2PO_4$ solution. The P desorption Q/I curves were obtained by a procedure using anion exchange resin beads and described by an empirical equation ($Q=aI^{-1}+bln(I+1)+c$). The P desorption Q/I curves for the high available P (${\g}20mg\;kg^{-1}$ of Olsen P) soils were characteristic concave trends with or without soil P enrichment, whereas for the low available P (${\lt}20mg\;kg^{-1}$ of Olsen P) soils, the anticipated Q/I concave curves could not be obtained without a proper amount of P addition. When the soils were enriched in phosphates, the values of desorbed solid phase labile P and solution P, such as $Q_{max}$ and $I_0$ respectively, were increased, but the ratio of $Q_{max}$ versus $I_0$ was decreased. Thus, the slope of desorption Q/I curve represented as phosphorus buffering power, $|BP_0|$, is decreased. The $|BP_0|$ values of the high available P soils ranged between 48 and $61L\;kg^{-1}$ in the P untreated samples and between 18 and $44L\;kg^{-1}$ in the P enriched samples. Overall $|BP_0|$ values of both low and high available P soils treated with $l00mg\;P\;kg^{-1}$ ranged between 14 and $79L\;kg^{-1}$. The $Q_{max}$, values ranged between 71.4 and $173.1mg\;P\;kg^{-1}$, and the lo values ranged between 0.98 and $3.82mg\;P\;L^{-1}$ in the P enriched soils. The $Q_{max}$ and $I_0$ values that control the P buffering power may be not specifically related to a specific soil property, but those values were complicatedly related to soil pH, clay content, soil organic matter content, and lime. Also, phosphorus release activity, however, markedly depended on the desorbability of the applied P as well as the native labile P.

Bioequivalence of Burophil Capsule to Surfolase Capsule (Acebrophylline 100 mg) (설포라제 캡슐(아세브로필린 100 mg)에 대한 부로필 캡슐의 생물학적 동등성)

  • Cho, Hea-Young;Park, Eun-Ja;Kang, Hyun-Ah;Kim, Se-Mi;Park, Chan-Ho;Oh, In-Joon;Lim, Dong-Koo;Lee, Myung-Hee;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.35 no.3
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    • pp.179-185
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    • 2005
  • Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

Bioequivalence of SCD Zaltoprofen Tablet to Soleton® Tablet (Zaltoprofen 80 mg) (솔레톤 정(잘토프로펜 80 mg)에 대한 삼천당잘토프로펜 정의 생물학적동등성)

  • Kang, Hyun-Ah;Park, Sun-Ae;Kim, Dong-Ho;Kim, Hwan-Ho;Yun, Hwa;Kim, Kyng-Ran;Yoo, Hee-Doo;Park, Eun-Ja;Cho, Hye-Young;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.36 no.3
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    • pp.209-215
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    • 2006
  • Zaltoprofen, (2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid) is an NSAID with powerful anti-inflammatory effects as well as an analgesic action on inflammatory pain. The purpose of the present study was to evaluate the bioequivalence of two zaltoprofen tablets, $Soleton^{\circledR}$ (CJ Corp.) and SCD Zaltoprofen (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of zaltoprofen from the two zatoprofen formulations in vitro was tested using KP Vlll Apparatus ll method with various dissolution media. Twenty six healthy male subjects, $23.2{\pm}2.26$ years in age and$64.7{\pm}8.08$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 80 mg as zaltoprofen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of zaltoprofen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Soleton^{\circledR}$ were 6.33, 5.91 and 17.7% for $AUC_t$, $C_{max}$ and untransformed $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,log $1.01{\sim}1og\;1.11$ and log $0.928{\sim}1og\;1.18$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating SCD Zaltoprofen tablet was bioequivalent to $Soleton^{\circledR}$ tablet.

Astrometric Detectability of Parallax Effect in Gravitational Microlensing Events (중력렌즈 사건의 측성적 시차효과 검출에 대한 연구)

  • HAN CHEONGHO
    • Publications of The Korean Astronomical Society
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    • v.15 no.1
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    • pp.15-19
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    • 2000
  • The lens mass determined from the photometrically obtained Einstein time scale suffers from large uncertainty due to the lens parameter degeneracy. The uncertainty can be substantially reduced if the mass is determined from the lens proper motion obtained from astrometric measurements of the source image centroid shifts, ${\delta}{\theta}_c$, by using high precision interferometers from space-based platform such as the Space Interferometry Mission (SIM), and ground-based interferometers soon available on several 8-10m class telescopes. However, for the complete resolution of the lens parameter degeneracy it is required to determine the lens parallax by measuring the parallax-induced deviations in the centroid shifts trajectory, ${\Delta}{\delta}{\theta}_c$ aloe. In this paper, we investigate the detectabilities of ${\delta}{\theta}_c$ and ${\Delta}{\delta}{\theta}_c$ by determining the distributions of the maximum centroid shifts, $f({\delta}{\theta}_{c,max})$, and the average maximum deviations, $(<{\Delta}{\delta}_{c,max}>)$, for different types of Galactic microlensing events caused by various masses. From this investigation, we find that as long as source stars are bright enough for astrometric observations it is expected that $f({\delta}{\theta}_c)$ for most events caused by lenses with masses greater than 0.1 $M_\bigodot$ regardless of the event types can be easily detected from observations by using not only the SIM (with a detection threshold but also the ${\delta}{\theta}_{th}\;\~3{\mu}as)$ but also the ground-based interferometers $(with\;{\delta}{\theta}_{th}\;\~3{\mu}as)$. However, from ground-based observations, it will be difficult to detect ${\Delta}{\delta}{\theta}_c$ for most Galactic bulge self-lensing events, and the detection will be restricted only for small fractions of disk-bulge and halo-LMC events for which the deviations are relatively large. From observations by using the SIM, on the other hand, detecting ${\Delta}{\delta}{\theta}_c$ will be possible for majority of disk and halo events and for a substantial fraction of bulge self-lensing events. For the complete resolution of the lens parameter degeneracy, therefore, SIM observations will be essential.

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The Magnetic Characteristics and Microstructure of Mn-A1 System Alloys(1st Report) -Focused on the Mn-A1 Alloys- (Mn-Al계 합금의 열처리에 따른 미세조직 변화와 지기적 특성(제1보) -Mn-Al-Cu 합금을 중심으로-)

  • Pang, Man-Gyu;Yang, Hyun-Soo;Kwak, Chang-Sup
    • Journal of the Korean Society for Precision Engineering
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    • v.5 no.4
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    • pp.48-58
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    • 1988
  • This study was undertaken to observe the formation behavior of ferro- magnetic phase in Mn-Al-Cu Alloys. The alloy selected for this investigation was 70% Mn-29% Al-1% Cu. This pre-allyed pig was prepared to the cylinderical castings using an Induction furnace after homogenizing at $1100^{\circ}C$ for 2hr, the specimens were cooled by cooling methods. Subwequent isothermal heat treatments were followed at $550^{\circ}C$ for various periods of time at predetermined(1-1000min). The formation behavior of ferromagnetic phase was investigated by measurements of magnetic properties of the specimens at each stage of heat treatment, and optical microscopic esamination and X-Ray diffraction analyses were also employed. By this basic experimental results, the conclusions are as follows 1) In order to obtain much amount of ferromagnetic phase, the optimum average cooling rate was about 7.35-$16.4^{\circ}C$/sec($1100^{\circ}C$-$600^{\circ}C$). 2) We verified the decomposition of {\tau} phase to {\beta} -Mn and {\gamma} , as the specimens were homogenized at $1100^{\circ}C$ for 12hr, then heat-treased at $550^{\circ}C$ for 1-1000min. 3) A condition of optimum heat treatments in Mn-Al-Cu permanent mag-netic alloys showed that after homogenizing at $1100^{\circ}C$ for 2hr, the speciments were cooled in air or furnace(A) and subsequent heat treatments at $550^{\circ}C$ for 1-30min. The maximum magnetic properties were measured as follows: Air cooling; Br=1200(Gause), bHc=100(oe), (BH)max=0.07(MGOe) Furnace cooling(A);Br=950(Gauss), bhe=80(Oe), (BH)max=0.05(MGOe)

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