• Title/Summary/Keyword: time to $V_{max}$

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Pharmacokinetics of Antiviral Pyrimidine Analogs in Rats (흰쥐에서 피리미딘 계열 항감염성 약물의 체내동태)

  • Han, Kyu-Won;Jeong, Lak-Shin;Kim, Kil-Soo
    • Journal of Pharmaceutical Investigation
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    • v.30 no.2
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    • pp.113-118
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    • 2000
  • In order to assay the efficacy of newly synthesized antiviral compounds, pyrimidine analogs, pharmacokinetics of those were established as compared with already marketed zidovudine. Zidovudine (15, 20, 25 and 35 mg/kg), LJ142 (18.52 mg/kg) and LJ143 (15, 18.52 and 30 mg/kg) were administered orally and intravenously in rats, blood samples were collected post-injection(i.e., for 360 min) at appropriate time intervals. Those were analyzed by HPLC with UV detection at 265 nm. Pharmacokinetic parameters $(C_{max},\;T_{1/2},\;MRT,\;AUC,\;AUMC,\;Vd_{SS},\;Cl_t)$ were calculated. AUCs of zidovudine and LJ143 following I.V. dosing of $15{\sim}25\;mg/kg\;and\;15{\sim}18.18\;mg/kg$ were dose-independent. However, AUCs of zidovudine and LJ43 following I.V. dosing of $25{\sim}35\;mg/kg\;and\;18.18{\sim}30\;mg/kg$ were dose-dependent. The relative bioavailability of zidovudine, LJ142 and LJ143 following oral administration were 61.94, 46.44 and 78.24%, respectively.

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Pharmacokinetics of a New Histone Hl Protein (p961), an Arthritis-suppressing Agent, in Rats and Rabbits (항류마치스 효과를 갖는 새로운 히스톤 H1 단백질 (p961)의 흰쥐와 토끼에 대한 약물동태)

  • 우수경;윤민혁;이재흥;권광일
    • YAKHAK HOEJI
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    • v.45 no.4
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    • pp.378-386
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    • 2001
  • A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....

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The Treatment of Heavy Metal-cyanide Complexes Wastewater by Zn$^{+2}$/Fe$^{+2}$ Ion and Coprecipitation in Practical Plant (II) (아연백법 및 공침공정을 이용한 복합 중금속-시안착염 폐수의 현장처리(II))

  • Lee, Jong-Cheul;Lee, Young-Man;Kang, Ik-Joong
    • Journal of Korean Society of Environmental Engineers
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    • v.30 no.5
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    • pp.524-533
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    • 2008
  • Industrial wastewater generated in the electroplating and metal finishing industries typically contain toxic free and complex metal cyanide with various heavy metals. Alkaline chlorination, the normal treatment method destroys only free cyanide, not complex metal cyanide. A novel treatment method has been developed which destroys both free and complex metal cyanide as compared with Practical Plant(I). Prior to the removal of complex metal cyanide by Fe/Zn coprecipitation and removal of others(Cu, Ni), Chromium is reduced from the hexavalent to the trivalent form by Sodium bisulfite(NaHSO$_3$), followed by alkaline-chlorination for the cyanide destruction. The maximum removal efficiency of chromium by reduction was found to be 99.92% under pH 2.0, ORP 250 mV for 0.5 hours. The removal efficiency of complex metal cyanide was max. 98.24%(residual CN: 4.50 mg/L) in pH 9.5, 240 rpm with 3.0 $\times$ 10$^{-4}$ mol of FeSO$_4$/ZnCl$_2$ for 0.5 hours. The removal efficiency of Cu, Ni using both hydroxide and sulfide precipitation was found to be max. 99.9% as Cu in 3.0 mol of Na$_2$S and 93.86% as Ni in 4.0 mol of Na$_2$S under pH 9.0$\sim$10.0, 240 rpm for 0.5 hours. The concentration of residual CN by alkaline-chlorination was 0.21 mg/L(removal efficiencies: 95.33%) under the following conditions; 1st Oxidation : pH 10.0, ORP 350 mV, reaction time 0.5 hours, 2nd Oxidation : pH 8.0, ORP 650 mV, reaction time 0.5 hours. It is important to note that the removal of free and complex metal cyanide from the electroplating wastewater should be employed by chromium reduction, Fe/Zn coprecipitation and, sulfide precipitation, followed by alkaline-chlorination for the Korean permissible limit of wastewater discharge, where the better results could be found as compared to the preceding paper as indicated in practical treatment(I).

Effects of Atorvastatin on the Pharmacokinetics of Nicardipine after Oral and Intravenous Administration in Rats

  • Choi, Jun-Shik;Ha, Sung-Il;Choi, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.18 no.2
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    • pp.226-232
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    • 2010
  • The aim of this study was to investigate the effect of atrovasatatin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine to rats. Nicardipine was administered orally (12 mg/kg) or intravenously (i.v., 4 mg/kg) without or with oral administration of atrovasatatin (0.3 or 1.0 mg/kg) to rats. The effect of atorvastatin on the P-glycoprotein (P-gp) as well as CYP3A4 activity was also evaluated. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 48 ${\mu}M$. Compared to the controls (nicardipine alone), the area under the plasma concentration-time curve (AUC) of nicardipine was significantly (1.0 mg/kg, p<0.05) greater by 16.8-45.4%, and the peak plasma concentration ($C_{max}$) was significantly (1.0 mg/kg, p<0.05) higher by 28.0% after oral administration of nicardipine with atorvastatin, respectively. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.17- to 1.45-fold and the absolute bioavailability (A.B.) of nicardipine with atrovasatatin was significantly greater by 16.7-20.9% compared to that of the controls (14.3%). Compared to the i.v. control, atrovasatatin did not significantly change pharmacokinetic parameters of i.v. administration nicardipine. The enhanced oral bioavailability of nicardipine by atorvastatin suggests that CYP3A subfamily-mediated metabolism were inhibited in the intestine and/or in the liver rather than P-gp-mediated efflux of nicardipine. Based on these results, modification of nicardipine of dosage regimen is required in the patients. Human studies are required to prove the above hypothesis.

Pharmacokinetics of Recombinant Human Epidermal Growth Factor (DWP401) in Rats (재조합 인간 상피세포성장인자(DWP401)의 흰쥐에서의 약물동태)

  • Chung, Joo-Young;Koh, Yeo-Wook;Nam, Kwon-Ho;Cho, Jae-Youl;Park, Seung-Kook;Yu, Young-Ho;Kim, Jae-Hwan;Han, Kun;Park, Myung-Hwan;Shim, Chang-Koo
    • YAKHAK HOEJI
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    • v.41 no.3
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    • pp.328-334
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    • 1997
  • Pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), was studied using radioimmunoassay (RIA) and $^{125}I$-DWP401 in rats. When DWP401 was adm inistered i.v. at doses of 50 and 500 mcg/kg, the plasma DWP401 disappeared biiexponentially with terminal half life of 4.7 and 92.8 min. The $C_{max}$ and $T_{max}$ after s.c. administration of ti at doses of 50 and 500 ${\mu}g$/kg were determined to be 23.6 and 17.5 ng/ml at 50 ${\mu}g$/kg, and 261.4 ng/ml and 36.8 min, respectively. Both the total urinary and biliary recoveries of intact DWP401 2343 very low (<0.4%), probably due to its extensive degradation in the body. the concentration ratio of DWP401 between the organ and plasma decreased especially in the liver and kidney as the dose and time after the dose increased. For example, the liver/plasma and kidney/plasma concentration ratio of DWP401 at 2.5 min after i.v. doses of 50 ${\mu}g$/kg were comparable and much larger than unity. But, the ratio at 2.5 min after i.v. doses of 500${\mu}g$/kg was much larger in the kidney that in than in the liver. These results suggest that the systemic administration of DWP401 might be subject to rapid and extensive clearance from circulation within several hour after main distrbution to liver and kidney.

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Development of Automated Surface Inspection System using the Computer V (컴퓨터 비젼을 이용한 표면결함검사장치 개발)

  • Lee, Jong-Hak;Jung, Jin-Yang
    • Proceedings of the KIEE Conference
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    • 1999.07b
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    • pp.668-670
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    • 1999
  • We have developed a automatic surface inspection system for cold Rolled strips in steel making process for several years. We have experienced the various kinds of surface inspection systems, including linear CCD camera type and the laser type inspection system which was installed in cold rolled strips production lines. But, we did not satisfied with these inspection systems owing to insufficient detection and classification rate, real time processing performance and limited line speed of real production lines. In order to increase detection and computing power, we have used the Dark Field illumination with Infra_Red LED, Bright Field illumination with Xenon Lamp, Parallel Computing Processor with Area typed CCD camera and full software based image processing technique for the ease up_grading and maintenance. In this paper, we introduced the automatic inspection system and real time image processing technique using the Object Detection, Defect Detection, Classification algorithms. As a result of experiment, under the situation of the high speed processed line(max 1000 meter per minute) defect detection is above 90% for all occurred defects in real line, defect name classification rate is about 80% for most frequently occurred 8 defect, and defect grade classification rate is 84% for name classified defect.

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Lipoxygenase Activity of Milled Fractions from Brown Rice (현미 도정획분의 Lipoxygenase 활성)

  • Kim, Ki-Joong;Rhee, Chong-Ouk
    • Korean Journal of Food Science and Technology
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    • v.29 no.1
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    • pp.145-149
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    • 1997
  • Lipoxygenase activity from brown rice varieties (Tongjinbyeo, Kumohbyeo and Kanchukbyeo) was investigated using spectrophotometric method. In all three varieties, there was an increase in the enzyme activity with the reaction time. Enzyme activity was tested at different concentration of the substrate. The $V_{max}\;and\;K_m$ values of Tongjin, Kumoh and Kanchukbyeo were 57.89, 19.85 and 31.38 units/mg protein and 0.054, 0.045 and 0.035 mM. The study of lipoxygenase activity at different pH levels showed that all the varieties had maximal activities around $pH\;7.0{\sim}7.6$. The enzyme activity and specific activity on milled fractions of different brown rice varieties, fraction II was superior to the other fractions and fraction IV was inferior to the other fractions. As the result of microwave heating for 0, 30, 60 and 90 sec, the enzyme activity and specific activity of all the varieties were decreased by the elapse of heating time.

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Pharmacokinetic-Pharmacodynamic Modeling for the Relationship between Glucose-Lowering Effect and Plasma Concentration of Metformin in Volunteers

  • Lee, Shin-Hwa;Kwon, Kwang-il
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.806-810
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    • 2004
  • Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

Chitosanolytic Characteristics of Cellulases from Trichoderma viride and Trichoderma reesei (Trichoderma viride 및 Trichoderma reesei 유래 Cellulase의 키토산 분해 특성)

  • Hong, Sang-Pill;Kim, Dong-Soo
    • Korean Journal of Food Science and Technology
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    • v.30 no.2
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    • pp.245-252
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    • 1998
  • The chitosanolytic capabilities of cellulases, glucosidases, proteases and commercial enzymes were evaluated, and effective chitosanolytic cellulases from T. viride, T. reesei and Celluclast, a commercial enzyme from T. reesei were characterized. The reaction of cellulase from T. viride, T. reesei and Celluclast was optimal at pH 5. 0 and $45{\sim}55^{\circ}C$. Max. chitosanolytic activities of cellulases from both T. viride and T. reesei were observed at the enzyme/chitosan ratio=0.1 and chitosan concentration=3.0%. For the possible application of commercial Celluclast to chitosan oligosaccharides production, 3%(w/v) chitosan was reacted with 1%(v/v) Celluclast at pH 5.0 and $55^{\circ}C$. The apparent viscosity decreased by 98% within 30 minutes reaction and Max. contents of 50% EtOH solubles were 70% at 15 hrs reaction. Total reducing sugars were also increased with reaction time and maintained approx. 13.5% after 2hrs reaction. In 15 hrs treated chitosan hydrolyzates, various kinds of chitosan oligosaccharides were produced and contents of chitosan hexamer, known for its antitumor activities, were about 8.0%, about 4 times higher values compared with acid hydrolysis method. The results suggested that chitosan oligosaccharides could be produced with low-cost cellulases from T. reesei.

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Estimation of the Reach-average Velocity of Mountain Streams Using Dye Tracing (염료추적자법을 이용한 산지하천의 구간 평균 유속 추정)

  • Tae-Hyun Kim;Jeman Lee;Chulwon Lee;Sangjun Im
    • Journal of Korean Society of Forest Science
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    • v.112 no.3
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    • pp.374-381
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    • 2023
  • The travel time of flash floods along mountain streams is mainly governed by reach-average velocity, rather than by the point velocity of the locations of interest. Reach-average velocity is influenced by various factors such as stream geometry, streambed materials, and the hydraulic roughness of streams. In this study, the reach-average velocity in mountain streams was measured for storm periods using rhodamine dye tracing. The point cloud data obtained from a LiDAR survey was used to extract the average hydraulic roughness height, such as Ra, Rmax, and Rz. The size distribution of the streambed materials (D50, D84) was also considered in the estimation of the roughness height. The field experiments revealed that the reach-average velocities had a significant relationship with flow discharges (v = 0.5499Q0.6165 ), with an R2 value of 0.77. The root mean square error in the roughness height of the Ra-based estimation (0.45) was lower than those of the other estimations (0.47-1.04). Among the parameters for roughness height estimation, the Ra -based roughness height was the most reliable and suitable for developing the reach-average velocity equation for estimating the travel time of flood waves in mountain streams.