• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.63-68
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• 2006

Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to ${\gamma}-aminobutyric$ acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced $2{\times}2$ crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. $WinNonlin^{(R)}$, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by $1/(predieted\;y)^2$ was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters $(AUC_{0-24hr},\;AUC_{inf},\;C_{max}\;and\;T_{max})$ and other parameters $(K_a,\;K_{el},\;V_d/F\;and\;Cl/F)$ of $Gapentin^{TM}$ (test drug) and $Neurontin^{TM}$ (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed $AUC_{0-24hr}\;and\;C_{max}$ were $log(0.9106){\sim}log(1.l254)\;and\;log(0.8521){\sim}log(1.0505)$, respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.513-518
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• 1998

Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

• Journal of Acupuncture Research
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• v.29 no.3
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• pp.81-88
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• 2012

Objectives : The purpose of this study was to assess the effect of Taegeuk acupuncture on reducing mental stress by analyzing heart rate variability in Soyangin. Methods : Eight Soyangin-diagnosed women participated in this study. They were randomly divided into group A and group B. Each participant went through 3 sessions every week with 1 week of washout period in between each session. HRV was measured three times at every session; at baseline, after administering mentally stressful circumstances and after applying either one of simple rest, Soyangin Taegeuk acupuncture or Soeumin Taegeuk acupuncture. This study was designed as a crossover clinical trial. After same initial simple resting session for both groups at week 1, acupuncture for group A were executed in the order of Soyangin Taegeuk acupuncture and Soeumin Taegeuk acupuncture at week 2 and 3 respectively, with acupuncture for group B conducted in reverse order. Results : Simple rest and Soeumin Taegeuk acupuncture did not show the significant changes in response to LF(norm) and HF(norm) after stress stimuli. Soyangin Taegeuk acupuncture did, however, significantly decrease LF(norm) and increase HF(norm). Soyangin Taegeuk acupuncture, compared to Soeumin Taegeuk acupuncture, significantly stabilized autonomic nervous system. Conclusions : This study suggests that Soyangin Taegeuk acupuncture might be an effective means of stabilizing mental stress-induced imbalance of autonomic nervous system for Soyangin.

• Journal of Acupuncture Research
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• v.30 no.4
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• pp.87-94
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• 2013

Objectives : The purpose of this study was to assess the effect of Taegeuk acupuncture on reducing mental stress by analyzing heart rate variability in Taeeumin. Methods : 16 Taeeumin-diagnosed healthy participated in this study. They were randomly divided into group A and group B. Each participant went through 3 sessions every week with 1 week of washout period in between each session. HRV was measured three times at every session; at baseline, after administering mentally stressful circumstances and after applying either one of simple rest, Taeeumin Taegeuk acupuncture or soyangin Taegeuk acupuncture. This study was designed as a crossover clinical trial. After same initial simple resting session for both groups at week 1, acupuncture for group A were executed in the order of Taeeumin Taegeuk acupuncture and soyangin Taegeuk acupuncture at week 2 and 3 respectively, with acupuncture for group B conducted in reverse order. Results : Simple rest, Taeeumin Taegeuk acupuncture and Soyangin Taegeuk acupuncture did show the significant changes in decrease LF(Norm) and increase HF(Norm) after stress stimuli. Taeeumin Taegeuk acupuncture, compared to Soyangin Taegeuk acupuncture, significantly decreased LF(Norm) and increased HF(Norm). Conclusions : This study suggests that Taeeumin Taegeuk acupuncture might be an effective means of stabilizing mental stress-induced imbalance of autonomic nervous system for Taeeumin.

• Journal of the Korean Institute of Intelligent Systems
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• v.16 no.2
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• pp.131-137
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• 2006

In swarm robot systems, each robot must behaves by itself according to the its states and environments, and if necessary, must cooperates with other robots in order to carry out a given task. Therefore it is essential that each robot has both learning and evolution ability to adapt the dynamic environments. In this paper, the new learning and evolution method based on reinforcement learning having delayed reward ability and distributed genetic algorithms is proposed for behavior learning and evolution of collective autonomous mobile robots. Reinforcement learning having delayed reward is still useful even though when there is no immediate reward. And by distributed genetic algorithm exchanging the chromosome acquired under different environments by communication each robot can improve its behavior ability. Specially, in order to improve the performance of evolution, selective crossover using the characteristic of reinforcement learning is adopted in this paper. we verify the effectiveness of the proposed method by applying it to cooperative search problem.

• Journal of the Korean Institute of Intelligent Systems
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• v.17 no.5
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• pp.591-597
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• 2007

In swarm robot systems, each robot must behaves by itself according to the its states and environments, and if necessary, must cooperates with other robots in order to carry out a given task. Therefore it is essential that each robot has both learning and evolution ability to adapt the dynamic environments. In this paper, the new polygon based Q-learning algorithm and distributed genetic algorithms are proposed for behavior learning and evolution of collective autonomous mobile robots. And by distributed genetic algorithm exchanging the chromosome acquired under different environments by communication each robot can improve its behavior ability Specially, in order to improve the performance of evolution, selective crossover using the characteristic of reinforcement learning is adopted in this paper. we verify the effectiveness of the proposed method by applying it to cooperative search problem.

• Membrane Journal
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• v.12 no.4
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• pp.247-254
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• 2002

In order to develop the ion exchange membranes which would be used in direct methanol fuel cell (DMFC), the polysulfone polymer was sulfonated using chlorosulfonic acid (CSA) and trimethylchlorosilane(TMCS). It has been characterized in terms of ion conductivities, methanol crossover, swelling degree and ion exchange capacities for the heat untreated and treated membranes at $150^{\circ}C.$ Typically, the methanol permeability and ion conductivity at the mole ratio of 1.4 between polysulfone repeating unit and sulfonating agents showed $2.87{\times}10^{-7}\; cm^2/s$(without heat treatment), $1.52{\times}10^{-7}\; cm^2/s$(with heat treatment) and $1.10{\times}10^{-2}\; S/cm$(without heat treatment), $0.87{\times}10^{-2}\;$ S/cm(with heat treatment), respectively. After the mole ration of 1.4 both values indicated mild increase.

• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.51-53
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• 2003

This study was conducted to compare the bioavailability of a generic product of Sinil Atenolol Tablets (Sinil Pharmaceutical Co., Ltd., Korea) with the innovator product, $Tenormin^{\circledR}$ Tablets in 20 healthy Korean volunteers. The volunteers received a single 50 mg dose of each atenolol formulation according to a randomized, two-way crossover design. Plasma samples were obtained over a 24-hour interval, and atenolol concentrations were determined by HPLC with a fluorescence detector. From the plasma atenolol concentration vs time curves, the following parameters were compared: area under the plasma concentration-time curve (AUC), peak plasma concentration $(C_{max})$, time to reach peak plasma concentration $(T_{max})$, and terminal first order elimination half-life $(t_{1/2})$. No statistically significant difference was obtained between the $T_{max}$ values, and the logarithmic transformed AUC and $C_{max}$ values of the two products. The 90% confidence for the ratio of the logarithmically transformed AUC and $C_{max}$ values of Sinil Atenolol Tablets over those of $Tenormin^{\circledR}$ Tablets were calculated to be between 0.99 and 1.07, and 1.04 and 1.16, respectively; both were within the bioequivalence limit of 0.80-1.25. The mean of $T_{max}$ in $Tenormin^{\circledR}$ Tablet group was 3.68 hour, and that in Sinil Atenolol Tablet group was 3.65 hour. The values of $t_{1/2}$ between the two products were found comparable, and the mean $t_{1/2}$ values of $Tenormin^{\circledR}$ Tablets and Sinil Atenolol Tablets were 5.9 and 6.0 hour, respectively. Based on these results, it was concluded that Sinil Atenolol Tablets were comparable to $Tenormin^{\circledR}$ Tablets in both the rate and extent of absorption, indicating that Sinil Atenolol Tablets were bioequivalent to the reference product, $Tenormin^{\circledR}$ Tablets

• Composites Research
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• v.12 no.4
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• pp.42-54
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• 1999

FMLC(Fiber-Metal Laminate Composites) is a new structural material combining thin metal laminate with adhesive fiber prepreg, it nearly include all the advantage of metallic materials, for example: good plasticity, impact resistance, processibility, light weight and excellent fatigue properties. This research studied the optimum design of the FMLC subject to various loading conditions using genetic algorithm. The finite element method based on the shear deformation theory was used for the analysis of FMLC. Tasi-Hill failure criterion and Miser yield criterion were taken as fitness functions of the fiber prepreg and the metal laminate, respectively. The design variables were fiber orientation angles. In genetic algorithm, the tournament selection and the uniform crossover method were used. The elitist model was also used to be effective evolution strategy and the creeping random search method was adopted in order to approach a solution with high accuracy. Optimization results were given for various loading conditions and compared with CFRP(Carbon Fiber Reinforced Plastic). The results show that the FMLC is more excellent than the CFRP in point and uniform loading conditions and it is more stable to unexpected loading because the deviation of failure index is smaller than that of CFRP.