• YAKHAK HOEJI
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• v.44 no.3
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• pp.232-236
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• 2000

An intravenous pharmacokinetics for a new red cell substitute, PEG-hemoglobin SB1, was studied in SD rats. Total-hemoglobin and its metabolite methemoglobin in the plasma were determined using a spectrophotometer. The limit of quantitation was 0.01g/dL and the C.V for interday assay reproducibility was less than 6%. Upon intravenous administration of anticipated clinical dose, 10 ml(0.7 gHb)/kg, plasma concentration curve of total-hemoglobin was well described by one-compartment model. The $t_{\frac{1}{2}},{\;}CL_{t}$, Vd and $AUC^{0-48hr}$ were $8.23{\pm}0.96{\;}hr,{\;}0.06{\;}{\pm}{\;}0.01 {\;}dL/hr/kg,{\;}0.66{\pm}0.05{\;}dL/lg{\;}and{\;}13.6{\;}{\pm}{\;}1.01g{\cdot}hr/dL$, respectively, in male rats(n=5, $mean{\;}{\pm}{\;}SD$). Those parameters in female rats were $9.21{\;}\pm{\;}2.31{\;}hr,{\;}0.06{\;}{\pm}{\;}0.01{\;}dL/hr/kg,{\;}0.79{\pm}{\;}0.08{\;}dL/kg{\;}and{\;}13.0{\;}{\pm}{\;}2.36{\;}g{\cdot}hr/dL$, respectively. Similar kinetic profiles between males and females were also obtained from other parameters. Small amount of methemoglobin, an oxidative metabolite of SB1, was detected in the plasma of both sexes, where the $AUC^{0-48{\;}hr,m}$ and $t_{{\frac{1}{2}},m}$ were approximately $1.5{\;}g{\cdot}hr/dL$ and 20 hr, respectively. The present work provides a critical kinetic data for the effective clinical applications of PEG-hemoglobin SB1.

• Journal of fish pathology
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• v.21 no.2
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• pp.107-117
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• 2008

The pharmacokinetic properties of oxytetracycline (OTC) were studied after dipping and oral administration to cultured olive flounder, Paralichthys olivaceus (600 g). Plasma concentrations of OTC were determined after oral dosage (50, 100 and 200 mg/kg body weight) and dipping (50, 100 and 200 ppm, 1 h) in olive flounder (average 600 g, 23±1℃). Plasma samples were taken at 3, 5, 10, 15, 24, 32, 48, 72, 120, 168 and 240 h post-dose. In oral dosage of 50, 100 and 200 mg/kg, the peak plasma concentrations of OTC, which attained at 3 h post-dose, were 0.34, 0.44 and 1.18 ㎍/㎖, respectively. In dipping of 50, 100 and 200 ppm, those of OTC which also observed at 5 h post-dose, were 0.43, 0.38 and 0.64 ㎍/㎖, respectively. Plasma concentrations of OTC were not measurable at 240 h post-dose in all experiments. The kinetic profile of absorption, distribution and elimination of OTC in plasma were analyzed fitting to a one-compartment model by WinNonlin program. The following parameters were calculated for a single dosage of 50, 100 and 200 mg/kg body weight, respectively: AUC (the area under the concentration-time curve)=31.40, 28.07 and 32.97 ㎍∙h/㎖; T1/2 (half-life)􀆫0.89, 1.12 and 0.43 h; Tmax (time for maximum concentration)= 5.25, 3.70 and 7.30 h, Cmax (maximum concentration)=0.25, 0.38 and 0.61 ㎕/㎖. Following dipping at 50, 100 and 200 ppm, these parameters were AUC􀆫15.51, 14.63 and 19.72 ㎍∙h/㎖; T1/2= 0.75, 0.41 and 0.74 h; Tmax=4.90, 7.08 and 4.68 h, Cmax=0.40, 0.32 and 0.46 ㎕/㎖.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.166-171
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• 2018

Although there are many commercially available training software programs for pharmacokinetics, they lack flexibility and convenience. In this study, we develop simulation software to facilitate pharmacokinetics education. General formulas for time courses of drug concentrations after single and multiple dosing were used to build source code that allows users to simulate situations tailored to their learning objectives. A mathematical relationship for a 1-compartment model was implemented in the form of differential equations. The concept of population pharmacokinetics was also taken into consideration for further applications. The source code was written using R. For the convenience of users, two types of software were developed: a web-based simulator and a standalone-type application. The application was built in the JAVA language. We used the JAVA/R Interface library and the 'eval()' method from JAVA for the R/JAVA interface. The final product has an input window that includes fields for parameter values, dosing regimen, and population pharmacokinetics options. When a simulation is performed, the resulting drug concentration time course is shown in the output window. The simulation results are obtained within 1 minute even if the population pharmacokinetics option is selected and many parameters are considered, and the user can therefore quickly learn a variety of situations. Such software is an excellent candidate for development as an open tool intended for wide use in Korea. Pharmacokinetics experts will be able to use this tool to teach various audiences, including undergraduates.

• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.49-54
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• 1999

This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

• Journal of fish pathology
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• v.24 no.1
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• pp.29-37
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• 2011

Effects of temperature ($13{\pm}1.5^{\circ}C$, $23{\pm}1.5^{\circ}C$) on the pharmacokinetic properties of nalidixic acid (NA) and piromidic acid (PA) were studied after oral administration to cultured black rockfish, Sebastes schlegeli. Serum concentrations of NA and PA were determined using HPLC-UV detector after a single dosage of 60 mg/kg body weight. At $23{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 24 h post-dose, were 5.87 and $0.43\;{\mu}g/ml$, respectively. At $13{\pm}1.5^{\circ}C$, the peak serum concentrations of NA and PA, which attained at 10 h post-dose, were 6.22 and $1.57\;{\mu}g/ml$, respectively. Better absorption of PA was noted at $13{\pm}1.5^{\circ}C$ compared to $23{\pm}1.5^{\circ}C$. However, absorption of NA was not affected significantly by temperature. The elimination of NA and PA from serum of black rockfish was considerably faster at $23{\pm}1.5^{\circ}C$ than at $13{\pm}1.5^{\circ}C$. The kinetic profile of absorption, distribution and elimination of NA and PA in serum were analyzed by fitting to a one compartment model, with WinNonlin program. The AUC, $T_{1/2}$, $T_{max}$ and $C_{max}$, respectively, were: $161.25\;{\mu}g{\cdot}h/ml$, 0.15 h, 12.29 h and $8.91\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $134.12{\mu}g{\cdot}h/ml$, 0.18 h, 8.79 h and $5.00\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with NA; $41.57\;{\mu}g{\cdot}h/ml$, 0.58 h, 8.24 h and $0.21\;{\mu}g/ml$ at $23{\pm}1.5^{\circ}C$, and $40.36\;{\mu}g{\cdot}h/ml$, 0.59 h, 5.04 h and $1.20\;{\mu}g/ml$ at $13{\pm}1.5^{\circ}C$ with PA.

• Journal of fish pathology
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• v.22 no.2
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• pp.125-135
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• 2009

The pharmacokinetic properties of oxolinic acid (OA) were studied after oral administration, intraperitoneal injection and dipping to cultured olive flounder, Paralichthys olivaceus (average 90 g, $23{\pm}1{^{\circ}C}$). Plasma samples were taken at 3, 5, 10, 15, 24, 30, 48, 96 and 144 h post-dose. In oral dosage at 15, 30 and 60 ㎎/㎏, the peak plasma concentrations of OA, which attained at 10~15 h post-dose, were 1.92, 2.45 and 3.72 $\mu{g}/m\ell$, respectively. In intraperitoneal injection with 10 and 20 ㎎/㎏, the peak plasma concentrations of OA, which attained at 10 h post-dose, were 4.1 and 4.8 $\mu{g}/m\ell$, respectively. In dipping in 30 and 50 ppm for 1 h, peak concentrations were observed at 5 h and 30 h post-dose, were 0.22 and 0.38 $\mu{g}/m\ell$, respectively. The kinetic profile of absorption, distribution and elimination of OA in plasma were analyzed fitting to a one-compartment model by WinNonlin program. Calculated parameters for a single oral dosage of 15, 30 and 60 ㎎/㎏, respectively, were: AUC (the area under the concentration-time curve)=70.93, 120.0 and 141.86 $\mu{g}$ $h/m\ell$ $T_{max}$ (time for maximum concentration)=16.22, 20.39 and 17.33 h; $C_{max}$ (maximum concentration)=���D1.61, 2.40 and 3.01 $\mu{g}/m\ell$. Following intraperitoneal injection of 10 and 20 ㎎/㎏, these parameters were AUC=184.7 and 315.92 $\mu{g}$ $h/m\ell$ $T_{max}$=5.91 and 6.26 h; $C_{max}$=4.19 and 4.45 $\mu{g}/m\ell$. Following dipping at 30 and 50 ppm, these parameters were AUC=17.58 and 21.69 $\mu{g}$ $h/m\ell$ $T_{max}$=19.08 and 31.43 h; $C_{max}$x=0.22 and 0.25 $\mu{g}/m\ell$.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.32-49
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• 1998

For estimation of regional myocardial blood flow with O-15 water PET, a few modifications considering partial volume effect based on single compartment model have been proposed. In this study, we attempted to quantify the degree of heterogeneity and to show the effect of tissue flow heterogeneity on partition coefficient(${\lambda}$) and to find the relation between perfusable tissue index(PTI) and ${\lambda}$ by computer simulation using two modified models. We simulated tissue curves for the regions with homogeneous and heterogeneous blood flow over a various flow range(0.2-4.0ml/g/min). Simulated heterogeneous tissue composed of 4 subregions of the same or different size of block which have different homogeneous flow and different degree of slope of distribution of blood flow. We measured the index representing heterogeneity of distribution of blood flow for each heterogeneous tissue by the constitution heterogeneity(CH). For model I, we assumed that tissue recovery coefficient ($F_{MME}$) was the product of partial volume effect($F_{MMF}$) and PTI. Using model I, PTI, flow, and $F_{MM}$ were estimated. For model II, we assumed that partition coefficient was another variable which could represent tissue characteristics of heterogeneity of flow distribution. Using model II, PTI, flow and ${\lambda}$ were estimated. For the simulated tissue with homogeneous flow, both models gave exactly the same estimates, of three parameters. For the simulated tissue with heterogeneous flow distribution, in model I, flow and $F_{MM}$ were correctly estimated as CH was increased moderately. In model II, flow and ${\lambda}$ were decreased curvi-linearly as CH was increased. The degree of underestimation of ${\lambda}$ obtained using model II, was correlated with CH. The degree of underestimation of flow was dependent on the degree of underestimation of ${\lambda}$. PTI was somewhat overestimated and did not change according to CH. We conclude that estimated ${\lambda}$ reflect the degree of tissue heterogeneity of flow distribution. We could use the degree of underestimation of ${\lambda}$ to find the characteristic heterogeneity of tissue flow and use ${\lambda}$ to recover the underestimated flow.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.2
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• pp.985-992
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• 2011

The 3D computational fluid dynamics (CFD) was performed in relation to the internal fluid characteristics and flow distribution for the development of the most optimal model in the complex post-disposal device. As it is expected that a channeling (drift) would be made by the semi-dry reactor due to the large difference in the flow distribution by the compartment in the bag filter, a structural improvement should be urgently made for more uniformed flow distribution in the bag filter. Three types of modifications such as i) changing the plenum shape, ii) orifice install in the exit part of cleaned gas, iii) increasing the plenum number were established. From the results of computational fluid dynamics, it was revealed that the changing of plenum shape and orifice install in the exit part of cleaned gas was more reasonable than the increasing the plenum number because of the difficulties of retrofit. The complex post-disposal device, modified and supplemented with this analysis, integrated the semi-dry reactor and the bag filter in a single body, so it follows that the improvement can make the device compact, save the installation area, save the operation fee, and management more convenient.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.11 no.11
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• pp.4656-4663
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• 2010

In this study, the 3D computational fluid dynamics (CFD) was performed in relation to the internal fluid characteristics, flow distribution, air mean ages, and residence time for the development of the most optimal model in the complex post-disposal device. As it is expected that a channeling (drift) would be made by the semi-dry reactor due to the large difference in the flow distribution by the compartment in the bag filter, a structural improvement should be urgently made for more uniformed flow distribution in the bag filter. In addition, it showed the possibility that the velocity field and distribution characteristics of the residence time could be improved through a modification to inlet structure of the spray dryer reactor. The complex post-disposal device, modified and supplemented with this analysis, integrated the semi-dry reactor and the bag filter in a single body, so it follows that the improvement can make the device compact, the installation area, the operation fee, and management more convenient.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.1-7
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• 1987

The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.