• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.66-70
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• 1999

The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration $(C_{max})$ of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

• Fire Science and Engineering
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• v.14 no.3
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• pp.6-12
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• 2000

This paper describes the smoke movement of a fire field model based on a self-developed SMEP(Smoke Movement Estimating Program) code to the simulation of fire induced flows in the two types of compartment space containing the radiation effect under smoke movement in room fire. The SMEP using PISO algorithm solves conservation equations for mass, momentum, energy and species, together with those for the modified k-$\varepsilon $ turbulence model with buoyancy term. Also it solves the radiation equation using the discrete ordinates method. The result of the calculated smoke temperature containing radiation effect has shown reasonable agreement compared with the experimental data. On the other hand, a difference of a lot was found between the temperature predicted by the SMEP with only convection effect and obtained by the experimental result. This seems to come from the radiation effect of $H_2$O and $CO_2$ gas under smoke productions. Thus, the consideration of the radiation effect under smoke in fire may be necessary in order to produce more realistic result.

• Journal of Bio-Environment Control
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• v.8 no.3
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• pp.192-201
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• 1999

This study was aimed to introduce the measurement of $CO_2$ concentration and leaf area index in the phytotron for predicting the effect of CO.E, light and leaf area index on the instantaneous photosynthetic rate of sweet pepper with the existing ASKAM model. Measurements were made in 2 semi-closed phytotron compartments in which three different $CO_2$ concentrations were applied at random. Plants were grown on containers with circulating nutrient solution at 21$^{\circ}C$ and 80-95% relative humidity. The model estimates crop net $CO_2$ uptake for short time intervals during the day based on short-term data of daily radiation, temperature and $CO_2$ concentration. During the photosynthesis measurements, $CO_2$ concentrations in both compartments and in the basement were measured every minute. This was also done for the flow of pure $CO_2$ into the compartment, global radiation, photosynthetic active radiation inside the compartment, temperature and relative humidity. Crop growth models summarize our knowledge on crop behavior and have as such a wide range of applications in analysis, crop management and thus as a farm management tool.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.73-82
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• 1997

Regional myocardial blood flow (rMBF) can be noninvasively quantified using N-13 ammonia and dynamic positron emission tomography (PET). The quantitative accuracy of the rMBF values, however, is affected by the distortion of myocardial PET images caused by finite PET image resolution and cardiac motion. Although different methods have been developed to correct the distortion typically classified as partial volume effect and spillover, the methods are too complex to employ in a routine clinical environment. We have developed a refined method incorporating a geometric model of the volume representation of a region-of-interest (ROI) into the two-compartment N-13 ammonia model. In the refined model, partial volume effect and spillover are conveniently corrected by an additional parameter in the mathematical model. To examine the accuracy of this approach, studies were performed in 9 coronary artery disease patients. Dynamic transaxial images (16 frames) were acquired with a GE $Advance^{TM}$ PET scanner simultaneous with intravenous injection of 20 mCi N-13 ammonia. rMBF was examined at rest and during pharmacologically (dipyridamole) induced coronary hyperemia. Three sectorial myocardium (septum, anterior wall and lateral wall) and blood pool time-activity curves were generated using dynamic images from manually drawn ROIs. The accuracy of rMBF values estimated by the refined method was examined by comparing to the values estimated using the conventional two-compartment model without partial volume effect correction rMBF values obtained by the refined method linearly correlated with rMBF values obtained by the conventional method (108 myocardial segments, correlation coefficient (r)=0.88). Additionally, underestimated rMBF values by the conventional method due to partial volume effect were corrected by theoretically predicted amount in the refined method (slope(m)=1.57). Spillover fraction estimated by the two methods agreed well (r=1.00, m=0.98). In conclusion, accurate rMBF values can be efficiently quantified by the refined method incorporating myocardium geometric information into the two-compartment model using N-13 ammonia and PET.

• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.258-266
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• 2017

Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and to elucidate individual characteristics to affects alcohol's PK or PD including dissolved oxygen. Methods: Following multiple intakes of total 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser (Lion SD-400 $Alcolmeter^{(R)}$). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteen healthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-order absorption and Michaelis-Menten elimination kinetics. $K_a$, V/F, $V_{max}$, $K_m$ is $8.1hr^{-1}$, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced $V_{max}$ (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model of temporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory $E_{max}$ model. $K_{e0}$, $I_{max}$, $E_0$, $IC_{50}$ were $0.23hr^{-1}$, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested that this PK/PD model was robust and has good precision.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.254-263
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• 2021

Background: A chronic social defeat stress (CSDS) model has been proposed as relevant to stress-induced behavioral change in humans. In this study, we examined the effect of Korean Red Ginseng (KRG) on CSDS-induced mood disorders and protein expression in an animal model. Methods: To evaluate the effect of KRG on social defeat stress, test mice were exposed in the resident aggressor's home cage compartment for 14 days beginning 1 h after KRG treatment (10, 20, and 40 mg/kg, per oral (p.o.)). After the exposure, behavioral tests to measure anxiety, social interaction, and depression-like behavior were performed. To investigate the underlying mechanism, N-methyl-D-aspartate receptor expression levels in CSDS-induced mice were evaluated using Western blot analysis. Results: CSDS induced anxiety-like behaviors by decreasing central activity in the open-field test and open-arm approach in the elevated plus maze test and led to social avoidance behavior in the social interaction test. CSDS mice showed upregulated NR1, NR2A, and NR2B expression in the hippocampus. KRG 20 and 40 mg/kg ameliorated anxiety-like activities and KRG 20 mg/kg alleviated social avoidance by decreasing time in the corner zone. KRG treatment recovered CSDS-induced NR1, NR2A, and NR2B protein levels in the hippocampus. Conclusion: These results indicate that KRG has a therapeutic effect on CSDS-induced mood disorder by alleviating N-methyl-D-aspartate receptor overexpression in the hippocampus.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.23 no.3
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• pp.108-114
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• 1997

The skin permeation study has two meanings in cosmetics. One is how to promote the skin permeation of active meterials for improving their bioavailabilities and the other is how to decrease it of irritants for reducing their skin side effects. In this study, we selected methyl paraben, one of the preservatives, as a model irritant and tried to reduce the skin irritation by the decrease of skin permeation. Furthermore, the relationship between skin permeation and skin primary irritation was discussed. For in vitro skin permeation experiments, Franz type diffusion cells and the excised skin of female hairless mouse from 8 weeks old were used. The donor compartment was charged with oil only or O/W emulsion containing 0.3% MP. We selected 19 oils, including esters, triglycerides, plant oils, hydrocarbons, and alchols, which are broadly used in cosmetics. We evaluated with female guinea pig. The skin permeahility of MP from the oils showed following order: ester oils > triglycerides > plant oils > hydrocarbons > alcohols. We considered that this result was based on the different effect of each oil on the barrier function of stratum corneum. In O/W emulsion containing each oil, the skin permeability of MP decreased as the oil/water partition coefficient of MP increased. The skin primary irritation increased as the skin permeability of MP increased. In conclusion, we suggest that the skin irritation could be reduced by the decrease of skin permeability of MP, which may be obtained by the good selection of oils in cosmetic preparations.

• Journal of the Korean Society for Precision Engineering
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• v.25 no.12
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• pp.117-124
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• 2008

In early design stage, the simulation of interior noise is useful for the enhancement of the noise, vibration and harshness (NVH) performance in a vehicle. The traditional transfer path analysis (TPA) technology cannot simulate the interior noise since it uses the experimental method. In order to solve this problem, in this paper, the hybrid TPA is developed as the novel approach. The hybrid TPA uses the simulated excitation force as the input force, which excites the flexible body of a car at the mount point, while the traditional TPA uses the measured force. This simulated force is obtained by numerical analysis for the FE (finite element) model of a powertrain. The interior noise is predicted by multiplying the simulated force by the vibro-acoustic transfer function (VATF) of the vehicle. The VATF is the acoustic response in the compartment of a car to the input force at the mount point of the powertrain in the flexible car body. The trend of the predicted interior noise based on the hybrid TPA very well corresponds to the measured interior noise, although there is some difference due to not only the experimental error and the simulation error but also the effect of the air-borne path.

• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.247-251
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• 1991

Effects of aluminum magnesium hydroxide (A) and cimetidine (C) on the pharmacokinetics of minocycline (M) were investigated in female rats. Blood samples were collected at various time intervals until 36 hrs following oral dosing of drugs. Plasma minocycline concentrations were determined by HPLC. Control group (M), $T_1$ group (M+A), $T_2$ group (A+M after 2 hrs), $T_3$ group (M+A after 2 hrs), $T_4$ group (M+C) and $T_5$ group (C+M after 2 hrs) were divided to examine interaction of the drugs with minocycline. Plasma minocyline level-time curves were well described by two-compartment open model with first-order absorption in rats. Antacid treatment was associated with reduced of 71.0, 45.9, 35.7% in minocycline absorption rate $constant(K_{\alpha})$, maximum plasma $concentration(C_{max})$, and relative $bioavailability(F_{rel})$, respectively. Cimetidine treatment group exhibited no significant changes in plasma level-time curve when compared with control group and did not affect minocycline absorption as by any of these three parameters.