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Effect of Gamiondam-tang (GMODT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with GMODT 100 mg/kg with 2.5 hr-intervals -

  • Ryu, Eun-A;Kang, Su-Jin;Song, Chang-Hyun;Lee, Bong-Hyo;Choi, Seong-Hun;Han, Chang-Hyun;Lee, Young-Joon;Ku, Sae-Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.21 no.2
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    • pp.127-137
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    • 2017
  • Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.

Effect of Gongjindan-gamibang on the Pharmacokinetics Profiles of Sorafenib in Male SD Rats (2) - Single Oral Combination Treatment of Sorafenib 50mg/kg with Gongjindan-gamibang 100 mg/kg, 3.5hr-intervals with 7-day Repeated Treatment -

  • Lee, Chang Hyeong;Kim, Seung Mo;Kang, Su Jin;Park, Soo Jin;Song, Chang Hyun;Han, Chang Hyun;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.19 no.1
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    • pp.145-159
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    • 2015
  • Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

Effect of Gongjindan, a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (2) - Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg, 1.5hr-intervals with 7-day Repeated Treatment -

  • Kwon, Oh Dae;Chung, Dae-Kyoo;Park, Soo Jin;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.2
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    • pp.139-155
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    • 2013
  • Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

Pulse Width and Pulse Frequency Modulated Soft Commutation Inverter Type AC-DC Power Converter with Lowered Utility 200V AC Grid Side Harmonic Current Components

  • Matsushige T.;Ishitobi M.;Nakaoka M.;Bessyo D.;Yamashita H.;Omori H.;Terai H.
    • Proceedings of the KIPE Conference
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    • 2001.10a
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    • pp.484-488
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    • 2001
  • The grid voltage of commercial utility power source hi Japan and USA is 100rms, but in China and European countries, it is 200rms. In recent years, In Japan 200Vrms out putted single phase three wire system begins to be used for high power applications. In 100Vrms utility AC power applications and systems, an active voltage clamped quasi-resonant Inverter circuit topology using IGBTs has been effectively used so far for the consumer microwave oven. In this paper, presented is a half bridge type voltage-clamped high-frequency Inverter type AC-DC converter using which is designed for consumer magnetron drive used as the consumer microwave oven in 200V utility AC power system. This zero voltage soft switching Inverter can use the same power rated switching semiconductor devices and three-winding high frequency transformer as those of the active voltage clamped quasi-resonant Inverter using the IGBTs that has already been used for 100V utility AC power source. The operating performances of the voltage source single ended push pull type Inverter are evaluated and discussed for consumer microwave oven. The harmonic line current components In the utility AC power side of the AC-DC power converter operating at ZVS­PWM strategy reduced and improved on the basis of sine wave like pulse frequency modulation and sine wave like pulse width modulation for the utility AC voltage source.

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Robust Double Deadbeat Control of Single-Phase UPS Inverter (단상 UPS 인버터의 강인한 2중 데드비트제어)

  • 박지호;허태원;안인모;이현우;정재륜;우정인
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.15 no.6
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    • pp.65-72
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    • 2001
  • This paper deals with a novel full digital control of the single-phase PWM(Pulse Width Modulation) inviter for UPS(Uninterruptible Power Supp1y). The voltage and current of output filter capacitor as a state variable are the feedback control input. In the proposed scheme a double deadbeat control consisting of minor current control loop and major voltage control loop have been developed In addition, a second order deadbeat currents control which should be exactly equal to its reference in two sampling time without error and overshoot is proposed to remove the influence of the calculation time delay. The load current prediction is achieved to compensate the load disturbance. The simulation and experimental result shows that the proposed system offers an output voltage with THD(Total Harmonic Distortion) less than 5% at a full nonlinear load.

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Pharmacokinetic Propertiese of Entecavir 1 mg in Korean Healthy Volunteers (건강한 한국인 피험자에서 Entecavir 1 mg 제제의 약동학적 특성 평가)

  • Jeon, Ji-Young;Hwang, Min-Ho;Im, Yong-Jin;Kim, Yun-Jeong;Han, Su-Mi;Im, Sung-Hyuk;Chae, Soo-Wan;Kim, Min-Gul
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.3
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    • pp.224-227
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    • 2011
  • Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to evaluate the safety and pharmacokinetic profile after a single dose of entecavir 1 mg administration in Korean healthy male subjects. Eight volunteers were enrolled. After a single dose of 1 mg entecavir was orally administered, blood samples were collected at specific time intervals from 0-168 hours. The plasma concentrations of entecavir were determined by LC-MS/MS. The pharmacokinetic parameters were determined from the plasma concentration-time profiles. The mean values for $AUC_{last}$ and $AUC_{inf}$ were $14.84{\pm}7.81ng{\cdot}hr/mL$ and $20.71{\pm}8.80ng{\cdot}hr/mL$, respectively. The mean value for $C_{max}$ was $9.19{\pm}4.91ng/ml$ and median value for $t_{max}$ was 0.58 hr. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. The results are suggested to be useful in clinical trials of entecavir in Korean subject including bioequivalence study.

Compound Effect of Persistent Organic Pollutants on the Mortality of Marine Copepods (유기오염물질의 복합독성이 요각류 사망률에 미치는 영향)

  • Kang, Jung-Hoon;Kim, Woong-Seo
    • Ocean and Polar Research
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    • v.28 no.1
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    • pp.45-56
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    • 2006
  • This study investigated primarily the toxic effects of bis(tributyltin)oxide (TBT) and DDT (Dichlorodiphenyltrichloroethane) on the mortality of adult Acartia omorii and barnacle nauplii as well as the hatching rate of A. omorii. Subsequently, compound effects of TBT and DDT on the mortality of immature copepods were tested in order to assess whether or not synergistic influence existed in the mixture of sublethal concentration of two pollutants. Mortality of adult A. omorii increased as exposure concentration of DDT increased in the range of from 0.0001 to 1ppm. Egg hatching rate of the copepod showed no distinctive difference in the range between 0.1 and 10ppm, while barnacle nauplii showed abnormal motility of their appendages in the range of 0.0001 to 1 ppm. Mortality of adult A. omorii increased as TBT concentration increased within the range of 1 and 10 ppb, whereas egg hatching rate of the copepod showed no linear response to the same exposure range. Moreover, copepod nauplii were almost motionless even though copepod eggs hatched under the exposure condition of TBT $(0{\sim}10 ppb)$ and DDT $(0{\sim}10 ppm)$, respectively, suggesting that the nauplii are hard to develop into adult stage. On the basis of the sublethal concentration less than the 24-h $LC_{50}$, 0.001 ppm (DDT) and 2 ppb (TBT) were selected to confirm the compound effects of two pollutants on the mortality of immature copepods. Mortality of immature copepods under the condition of mixture of the two pollutants was higher than that in the single exposure condition. This result seems to indicate that synergistic effects of sublethal toxicants can make a more hazardous effect on the survival of immature copepods even though the concentration of single toxicant is not lethal to copepods in the marine environment.

Design of fuel cell power conversion system controlled by TMS32OC31 DSP Chip (TMS32OC31 DSP칩에 의해 제어되는 연료전지용 전력변환장치의 설계)

  • Mun, S.P.;Kwon, S.K.;Suh, K.Y.;Kim, Y.M.
    • Proceedings of the KIEE Conference
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    • 2006.04b
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    • pp.351-354
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    • 2006
  • Recently, a fuel cell with low voltage and high current output characteristics is remarkable for new generation system It needs both a DC-DC step-up converter and DC-AC inverter to be used in fuel cell generation system Therefor, this paper, consists of an isolated DC -DC converter to boost the fuel cell voltage 380[$V_{DC}$] and a PWM inverter with LC filter to convent the DC voltage to single phase 220[$V_{AC}$]. Expressly, a tapped inductor filter with freewheeling diode is newly implemented in the output filter of the proposed high frequency isolated ZVZCS PWM DC-DC converter to suppress circulating current under the wide output voltage regulation range, thus to eliminate the switching and transformer turn-on/off over-short voltage or transient phenomena Besides the efficiency of 93-97[%]is obtained over the wide output voltage regulation ranges and load variations.

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Holographic Polymer-Dispersed Liquid Crystals and Polymeric Photonic Crystals Formed by Holographic Photolithography

  • Kyu Thein;Meng Scott;Duran Hatice;Nanjundiah Kumar;Yandek Gregory R.
    • Macromolecular Research
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    • v.14 no.2
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    • pp.155-165
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    • 2006
  • The present article describes the experimental and theoretical observations on the formation of holographic, polymer-dispersed, liquid crystals and electrically switchable, photonic crystals. A phase diagram of the starting mixture of nematic liquid crystal and photo-reactive triacrylate monomer was established by means of differential scanning calorimetry (DSC) and cloud point measurement. Photolithographic patterns were imprinted on the starting mixture of LC/triacrylate via multi-beam interference. A similar study was extended to a dendrimer/photocurative mixture as well as to a single component system (tetra-acrylate). Theoretical modeling and numerical simulation were carried out based on the combination of Flory-Huggins free energy of mixing and Maier-Saupe free energy of nematic ordering. The combined free energy densities were incorporated into the time-dependent Ginzburg-Landau (Model C) equations coupled with the photopolymerization rate equation to elucidate the spatio-temporal structure growth. The 2-D photonic structures thus simulated were consistent with the experimental observations. Furthermore, 3-D simulation was performed to guide the fabrication of assorted photonic crystals under various beam-geometries. Electro-optical performance such as diffraction efficiency was evaluated during the pattern photopolymerization process and also as a function of driving voltage.

Design of A 1.8-V CMOS Frequency Synthesizer for WCDMA

  • Lee, Young-Mi;Lee, Ju-Sang;Ju, Ri-A;Jang, Bu-Cheol;Yu, Sang-Dae
    • Proceedings of the IEEK Conference
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    • 2002.07b
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    • pp.1312-1315
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    • 2002
  • This research describes the design of a fully integrated fractional-N frequency synthesizer intended for the local oscillator in IMT-2000 system using 0.18-$\mu\textrm{m}$ CMOS technology and 1.8-V single power supply. The designed fractional-N synthesizer contains following components. Modified charge pump uses active cascode transistors to achieve the high output impedance. A multi-modulus prescaler has modified ECL-like D flip-flop with additional diode-connected transistors for short transient time and high frequency operation. And phase-frequency detector, integrated passive loop filter, LC-tuned VCO having a tuning range from 1.584 to 2.4 ㎓ at 1.8-V power supply, and higher-order sigma-delta modulator are contained. Finally, designed frequency synthesizer provides 5 ㎒ channel spacing with -122.6 dBc/Hz at 1 ㎒ in the WCDMA band and total output power is 28 mW.

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