• YAKHAK HOEJI
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• v.42 no.2
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• pp.181-186
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• 1998

This study was attempted to investigate the pharmacokinetics of cyclosporine (10mg/kg, oral) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. The area under the curve (AUC) of blood cyclosporine concentration versus time was significantly increased ($CCI_4$-induced hepatic disorder. Elimination rate constant (Kel) was significantly decreased (p<0.05, p<0.01) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. Volume of distribution (Vdss) and total body clearance (CLtot) were significantly decreased (p<0.01) in rabbits with $CCI_4$-induced hepatic disorder. But Vdss was significantly increased (p4-induced hepatic disorder were 874ng/ml and 2.71 hr, respectively. Cmax and Tmax values in rabbits with bile duct ligation were 105ng/ml and 2.834 hr, respectively. From results of this experiment. It is desirable to do therapeutic drug monitoring of cyclosporine for effective treatment when the cyclosporine is administered to patients with liver disorder m clinical practice.

• YAKHAK HOEJI
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• v.47 no.2
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• pp.98-103
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• 2003

The purpose of this study was to investigate the effect of flavone (20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (40 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with flavone was increased significantly (coadministration p＜0.05, pretreatment p＜0.0l) compared to that of control. Area under the plasma concentration-time curve (AVC) of paclitaxel with flavone was significantly (coadministration p＜0.05, pretreatment p＜0.0l) higher than that of control. Peak concentration (Cmax) of paclitaxel with flavone were significantly increased (coadministration p＜0.05, pretreatment p＜0.01) compared to that of control. Time to peak concentration (Tmax) of paclitaxel with flavone decreased significantly (p＜0.05) than that of control. The total body clearance (CLt) and elimination rate constant ($\beta$) of paclitaxel with flavone were significantly reduced (p＜0.05) compared to those of control. Half-life (t$_{1}$2/) of paclitaxel with flavone was significantly prolonged (p＜0.05) compared to that of control. Based on these results, it might be concluded that flavone may enhance bioavailability of paclitaxel through the inhibition of cytochrome P450 and P-glycoprotein, which are engaged in paclitaxel absorption and metabolism in liver and gastrogintestinal mucosa, respectively.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.269-275
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• 2000

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepato-protective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-micro-emulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyma $n^{R}$ 140 soft capsule). In this study, the pharmacokinetic profiles of Silyma $n^{R}$ were examined and compared it with a reference preparation, L Caps140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2$\times$2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The $C_{max}$ and AUC of the Silyma $n^{R}$ were 1542.0 $\pm$ 402.7 ng/ml and 3323.3 $\pm$ 824.7 ng.h/ml, respectively, and were significantly higher than those of reference preparation. The Tmax was 0.8 $\pm$ 0.3 h and significantly shorter than reference preparation. The $K_{e}$ and $T_{1}$2/ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for $C_{max}$, and -61.1% for $T_{max}$./.>././.>./.

• YAKHAK HOEJI
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• v.48 no.5
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• pp.278-284
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• 2004

In order to determine the bioavailability of c1onazepam, an anxiolytic drug, a simple, rapid and sensitive HPLC analysis was developed in healthy Korean volunteers. The analysis system was validated in specificity, accuracy, precision and linearity. The analysis condition we established was 2.58 min and 5 ng/$m\ell$ in retention time and limit of quantitation of c1onazepam, respectively, using reverse-phase C18 column connected to UV detector. Quantitation was performed at 235 nm wave length with p-hydroxybenzoic acid ethyl ester as internal standard. The method involved a simple extraction. In order to study blood level profiles as a function of time, eight volunteers were enrolled and orally took 6 mg clonazepam once. The blood samples were collected from 0 to 120 h after the drug administration. Mean AUC and Cmax value were 1028.17$\pm$568.165 (ng/$m\ell$$.$hr) and 41.25$\pm$10.82 (ng/$m\ell$), respectively. And mean Tmax and T$_{1}$2/ value were 1.08$\pm$0.42 (hr) and 30.78$\pm$3.26 (hr). From the results we determine the pharmacokinetic characteristics of clonazepam in Korean people using a newly developed and useful HPLC method.

• Journal of Information Processing Systems
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• v.18 no.3
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• pp.374-388
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• 2022

Database systems usually have many parameters that must be configured by database administrators and users. RocksDB achieves fast data writing performance using a log-structured merged tree. This database has many parameters associated with write and space amplifications. Write amplification degrades the database performance, and space amplification leads to an increased storage space owing to the storage of unwanted data. Previously, it was proven that significant performance improvements can be achieved by tuning the database parameters. However, tuning the multiple parameters of a database is a laborious task owing to the large number of potential configuration combinations. To address this problem, we selected the important parameters that affect the performance of RocksDB using random forest. We then analyzed the effects of the selected parameters on write and space amplifications using analysis of variance. We used a genetic algorithm to obtain optimized values of the major parameters. The experimental results indicate an insignificant reduction (-5.64%) in the execution time when using these optimized values; however, write amplification, space amplification, and data processing rates improved considerably by 20.65%, 54.50%, and 89.68%, respectively, as compared to the performance when using the default settings.

• Proceedings of the Korea Water Resources Association Conference
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• 2022.05a
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• pp.136-136
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• 2022

This study investigates the possibility of coupling empirical mode decomposition (EMD) for runoff prediction from machine learning (ML) models. Here, support vector regression (SVR) and convolutional neural network (CNN) were considered for ML algorithms. Precipitation (P), minimum temperature (Tmin), maximum temperature (Tmax) and their intrinsic mode functions (IMF) values were used for input variables at a monthly scale from Jan. 1973 to Dec. 2020 in the Grand river basin, Canada. The support vector machine-recursive feature elimination (SVM-RFE) technique was applied for finding the best combination of predictors among input variables. The results show that the proposed method outperformed the individual performance of SVR and CNN during the training and testing periods in the study area. According to the correlation coefficient (R), the EMD-SVR model outperformed the EMD-CNN model in both training and testing even though the CNN indicated a better performance than the SVR before using IMF values. The EMD-SVR model showed higher improvement in R value (38.7%) than that from the EMD-CNN model (7.1%). It should be noted that the coupled models of EMD-SVR and EMD-CNN represented much higher accuracy in runoff prediction with respect to the considered evaluation indicators, including root mean square error (RMSE) and R values.

• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.291-299
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• 1997

In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.122-127
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• 2001

4-tert-octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. Also, OP is known to have estrogenic activity by interacting with development and functions of endocrine system. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley rats. Male rats were administered OP, by either single oral (gavage) applications of 50, 100 or 200 mg/kg body weight. or a single intravenous injections of 1, 5 or 10 mg/kg body weight. Blood samples taken at several time intervals after administration were obtained from the femoral artery. Analysis of blood samples for OP was performed by gas chromatography mass spectrometry (GC/MS). The detection limit of OP was 1.9 ng/$m\ell$ at SIM (selected ion monitoring) mode of GC/MS. Calibration curve for analysis of the concentrations of OP in plasma was (OP/butylphenol peak area ratio) = 0.0294 $\times$ (plasma cone.) + 0.028 ($r^2$= 0.9991). The OP plasma concentration was 3921 ng/$m\ell$ immediately after single intravenous application, decreased rapidly within 45 min, and was detectable at low concentration up to 6 hr after application. When administered orally in rats (50, 100 and 200 mg/kg), OP was detected in the blood early after gavage administration, indicating the rapid initial uptake from gastrointestinal tract, with Tmax obtained from 0.67~0.83 hr. Using the AUC (area under the curve) of plasma concentration vs. time, low oral bioavailabilities of 1.2, 5.0 and 5.3% were calculated for the 50, 100 and 200 mg/kg groups, respectively.

• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.7-12
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• 2001

Cilostazol has both antithrombotic and cerebral vasodilating effects, and one of the mechanism is the selective inhibition of platalet cyclic AMP phosphodiesterase. Bioequivalence of two cilostazol tablets, the $Pletaal^{TM}$ (Korea Otsuka Pharmaceutical Co.) and the LG $Cilostazol^{TM}$ (LG Chemical Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers ($20\sim29$ years old) were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After oral administration of $Pletaal^{TM}$ or LG $Cilostazol^{TM}$ tablet (100 mg cilostazol), blood samples were taken at predetermined time intervals and the serum cilostazol concentrations were determined using an HPLC method with UV/VIS detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA was utilized for the statistical analysis. The results showed that the differences in AUCt, C_{max} and Tmax between two tablets based on the $Pletaal^{TM}$ tablet were $-5.39\%,\;2.32\%\;and\;4.26\%$, respectively. The powers (1-${\beta}$) for $AUC_t,\;C_{max}\;and\;T_{max}\;were\;83.81\%,\;96.02\%\;and\;91.04%$, respectively. Minimum detectable differences ($\Delta$) and $90\%$ confidence intervals were all less than $\pm20\%$. All these parameters met the criteria of KFDA for bioequivalence, indicating that LG $Cilostazol^{TM}$ tablet is bioequivalent to $Pletaal^{TM}$ tablet.

• Toxicological Research
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• v.23 no.2
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• pp.159-164
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• 2007

Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.