• Title/Summary/Keyword: Dosing

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Changes in the Pharmacokinetics of Rosiglitazone, a CYP2C8 Substrate, When Co-Administered with Amlodipine in Rats

  • Kim, Seon-Hwa;Kim, Kyu-Bong;Um, So-Young;Oh, Yun-Nim;Chung, Myeon-Woo;Oh, Hye-Young;Choi, Ki-Hwan
    • Biomolecules & Therapeutics
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    • v.17 no.3
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    • pp.299-304
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    • 2009
  • Rosiglitazone maleate (RGM) is widely used for improving insulin resistance. RGM is a moderate inhibitor of cytochrome P450 2C8 (CYP2C8) and is also mainly metabolized by CYP2C8. The aim of this study was to determine whether the effect of RGM on CYP2C8 is altered by co-treatment with other drugs, and whether amlodipine camsylate (AC) changes the pharmacokinetics (PK) of RGM. Of the 11 drugs that are likely to be co-administered with RGM in diabetic patients, seven drugs lowered the $IC_{50}$ value of RGM on CYP2C8 by more than 80%. In vitro CYP2C8 inhibitory assays of RGM in combination with drugs of interest showed that the $IC_{50}$ of RGM was decreased by 98.9% by AC. In a pharmacokinetic study, Sprague-Dawley (SD) rats were orally administered 1 mg/kg of RGM following by single or 10-consecutive daily administrations of 1.5 mg/kg/day of AC. No significant changes in the pharmacokinetic parameters of RGM were observed after a single administration of AC, but the AUC and $C_{max}$ values of RGM were significantly reduced by 36% and 31%, respectively, by multiple administrations of AC. In conclusion, RGM was found to be affected by AC by in vitro CYP2C8 inhibition testing, and multiple dosing of AC appreciably changed the pharmacokinetics of RGM. These findings suggest that a drug interaction exists between AC and RGM.

Evaluation of Peri-procedural Anticoagulation Drug Therapy undergoing Radiofrequency Ablation in Patients with Atrial Fibrillation (심방세동 환자의 고주파 도자절제술 전.후의 항응고약물요법 사용실태 분석)

  • Kim, Su-Hyun;An, Sung-Shim;Kim, Soon-Joo;Bang, Joon-Seok;La, Hyen-Oh
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.2
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    • pp.159-164
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    • 2010
  • Radiofrequency ablation (RA) is being used to manage atrial fibrillation (AF) with patients failed at the $1^{st}$-line anti-arrhythmic medications. Patients undergoing this procedure are at increased risk of thromboembolism after ablation, and anticoagulation management surrounding the ablation remains controversial. Although no conclusive recommendations can be made, published guidelines and data support therapeutic anticoagulation with warfarin. The purpose of this study was to analyze effectiveness of current therapy and to find factors fluctuate International Normalized Ratio (INR) values in patients undergone RA followed by anticoagulation service (ACS). Retrospective review was conducted utilizing database in a hospital. Among 110 patients under warfarin around ablation between January 2006 to September 2007, 54 patients were selected and allocated into 2 groups: Group A included 47 who discontinued warfarin after ablation, while 7 in B continued the medication. Information on demographics, amount and length of warfarin dosing, INR values and measuring frequencies, and the causing factors on INR fluctuation were abstracted. Differences were analyzed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. Mean amount of warfarin before and after surgery was 4.0 mg, 4.1 mg in Group A and was 5.1 mg, 4.6 mg in Group B, respectively. Average duration of warfarin doing before ablation was 73.7 days in Group A, 129.9 days in B with no significant difference (p = 0.312). The duration time of warfarin on groups after ablation lasted several months. The number of checking INRs was 4.1 and 7.6, respectively. Inter-individual variability of INR fluctuations were $2.1{\pm}0.6$ in Group A and $2.2{\pm}0.7$ in B which were not significantly different (p = 0.062). 164 cases of decreased INR were: 'omission in taking medication, stressfulness and headache, 'increased intake of high vitamin K foods', 'lifestyle change of increased physical activities', and 'increase of food-intakes'. To the contrary, 36 cases of increased INR were: 'reduce of food-intake', 'use of non-prescription drugs', 'reduction in physical activities', and 'excessive restriction on food-intake', consecutively. In conclusion, the study validated therapeutic outcomes of RA patients who we treated with standard guideline and demonstrated 9 factors of INR fluctuations in the patient. A well-trained, pharmacist-monitored anticoagulation service could reduce the risk of adverse effects and prevent complications in patients with AF around RA operation.

The Removal and Adsorption Characteristics of 2-MIB & Geosmin using PAC (PAC를 이용한 2-MIB와 Geosmin의 흡착특성과 제거에 관한 연구)

  • Jun, Dae-Young;Lee, Hyeon-Ju;Hong, Seongho;Yoon, Jeyong
    • Journal of Korean Society of Environmental Engineers
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    • v.22 no.11
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    • pp.2097-2104
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    • 2000
  • Naturally occurring taste and odor problems include those produced by microorganism. notably algae and bacteria. The major compounds causing taste and odor are MIB and Geosmin which can cause earthy-musty at very low concentration 9ng/L and 4ng/L, respectively. Especially, the problem is very serious from summer to fall in source and finished water. It is well known that using PAC is one of the best technology to control these compounds in drinking water treatment. In this study, optimum dosage and dosing time of PAC were observed with the adsorption isotherm experiments in single and binary compounds. Also, the effect of natural organic matter(NOM) was investigated by using a natural water with JSW. The adsorption capacity of Geosmin was higher than MIB in both with NOM and without NOM. The adsorption capacity of Geosmin and MIB was 4 times lower with NOM than that of without NOM. which was caused by competition adsorption. When the initial concentration of Geosmin and MIB were 100ng/L in JSW, at least 4 hours of reaction time was needed to achieve 99% removal with 20mg/L of the PAC.

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Biological Activity of Recombinant Human Erythropoietin (EPO) In Vivo and In Vitro

  • Park Jong-Ju;Lee Hyen-Gi;Nam In-Suk;Park Hee-Ja;Kim Min-Su;Chung Yun-Hi;Naidansuren Purevjargal;Kang Hye-Young;Lee Poong-Yun;Park Jin-Gi;Seong Hwan-Hoo;Chang Won-Kyong;Kang Myung-Hwa
    • Reproductive and Developmental Biology
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    • v.29 no.2
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    • pp.69-73
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    • 2005
  • The hematopoietic growth factor erythropoietin (EPO) is required for the maintenance, proliferation, and differentiation of the stem cells that produce erythrocytes. To analyse the biological activity of the recombinant human EPO (rec-hEPO), we have cloned the EPO cDNA and genomic DNA and produced rec-hEPO in the CHO cell lines. The growth and differentiation of EPO-dependent human leukemic cell line (F36E) were used to measure cytokine dependency and in vitro bioactivity of rec-hEPO. MIT assay values were increased by survival of F36E cells at 24h or 72h. The hematocrit and RBC values were increased by subcutaneous injection of 20 IU (in mice) and 100IU(in rats) rec-hEPO. Hematocrit values remarkably increased at $13.2\%$ (in mice) and $12.2\%$ (in rats). The pharmacokinetic behavior with injection of 6 IU of rec-hEPO remained detectable after 24 h in all mice tested. The highest peat appeared at 2h after injection. The long half-life of rec-hEPO is likely to confer clinical advantages by allowing less frequent dosing in patients treated for anemia. These data demonstratethat ree-hEPO produced in this study has a potent activity in vivo and in vitro. The results also suggest that biological activity of ree-hEPO could be remarkably enhanced by genetic engineering that affects the potential activity, including mutants with added oligosaccharide chain and designed to produce EPO-EPO fusion protein.

A Study on the Optimum Operating Condition of Acid Fermenter for the BNR Performance Improvement (BNR 효율개선을 위한 산 발효조 최적운전 조건에 관한 연구)

  • Kim, Hyo-Sang;Park, Jong-Woon;Seo, Jung-Won;Park, Chul-Hwi
    • Journal of Korean Society of Environmental Engineers
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    • v.22 no.3
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    • pp.587-595
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    • 2000
  • The most problems of domestic sewage for BNR(Biological Nutrients Removal) process are deficiency of carbon source and low C/N ratio. Primary sludge fermentation is seemed to be one of the best solutions producing biodegradable organic substrates. Soluble organic materials from sludge fermentation are mainly SCFAs(Short-Chain Fatty Acids) with 2~5 carbon atoms. In this research, it was attempted to apply $A_2/O$ process with the side-stream acid fermenter to improve the nutrients removal efficiency. The result showed that proper SCFAs production is about 3.000mg/L with SRT of 4~5 days. SCFAs yield of approximately 0.10~0.16 mg SCFAs(as COD) per mg of primary sludge(as COD) were achieved. The ratio of acetic. propionic. butyric and valerie acid were 1, 0.7, 0.5 and 0.6. Significant improvements of nutrients removal over 70% in BNR process were observed. thus will reduce the demand for chemical dosing to increase nutrients removal efficiency. When the fermentate was entered $A_2/O$ process, the ratio of phosphate release to substrate uptake amounts to $0.34gPO_4-Pg^{-1}COD$.

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Development of Optimum PAC Dose Prediction Program using $^{14}C$-radiolabled MIB and HSDM ($^{14}C$-radiolabeled MIB와 HSDM을 이용한 최적 PAC 투입량 예측프로그램의 개발)

  • Kim, Young-Il;Bae, Byung-Uk;Kim, Kyu-Hyoung;Hong, Hyun-Su;Westerhoff, Paul
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.10
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    • pp.1123-1128
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    • 2005
  • NIB(methylisoborneol) is an earthy/musty odor compound produced as a second metabolite by cyanobacteria and actinomycetes. MIB is not removed by conventional water treatment(coagulation, sedimentation, filtration) and its presence in tap water, even at low ng/L levels, can result in consumer complaints. PAC(powdered activated carbon) can effectively remove MIB when the correct dose is applied. But, since most operators in water treatment plants apply a PAC dose and then adjust that dose depending on direct observation (odor detection) after treatment, the result is often under-dose or eve,-dose. In this study, kinetic and isotherm tests using $^{14}C$-radiolabeled MIB were performed to determine coefficients for the HSDM(homogeneous surface diffusion model), including liquid film mass transfer coefficient($K_f$) and surface diffusion coefficient ($D_s$). The HSDM gave a reasonable fit and allowed prediction with the experimental data. Base on the HSDM, the authors developed an optimum PAC dose prediction program using the Excel spreadsheet. When the developed program was applied at two water treatment plants, the PAC dose based on the experience of operators in the water treatment plant was significantly different from that recommended by the newly developed program. If operators are willing to use the optimum PAC dose prediction program, it should solve dosing problems.

Effect of Inorganic Coagulants on the Performance of Electro-Chemical Treatment Process Treating Hospital Wastewater (병원폐수의 전기화학적 처리시 무기응집제 주입 효과에 관한 연구)

  • Jeong, Seung-Hyun;Jeong, Byung-Gon
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.10
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    • pp.709-716
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    • 2011
  • Effect of inorganic coagulants dosing on the performance of electro-chemical process was studied when treating hospital wastewater having low electrolyte concentration. It is thought that adding inorganic coagulants caused increase in concentration of electrolyte and this caused increase in free chloride concentration and consequently, caused increase in indirect oxidation effect. Thus, COD removal efficiencies more than doubled in percentage terms at the 2 hrs of reaction time and current density of $1.76A/dm^2$ compared with the results obtained from the parallel experiments without adding inorganic coagulants. T-N removal efficiencies approximately doubled in percentage terms at the 2 hrs of reaction time and 700 ppm of coagulants addition and applied current density of $1.76A/dm^2$ due to the increase of free residual chlorine such as HOCl caused by increase of electrolyte concentration through the addition of inorganic coagulants. Under the same experimental condition, more than 90% of T-P removal efficiencies was obtained. The reason can be explained that increase of chemical adsorption rate between phosphate and insoluble metal compounds caused by dissolved oxygen generated from anode by the increased electrolyte concentration through inorganic coagulants addition make a major role in improving T-P removal efficiencies. It can be concluded that inorganic coagulants addition as the supplemental agent of electrolyte is effective way in improving organic and nutrient salt removal efficiency when treating hospital wastewater having low electrolyte concentration.

Development of the Electrolysis Ballast Water Treatment System and Test (직접 전기분해식 선박평형수 처리장치 개발과 시험에 관한 연구)

  • Bag, Og-Yeol;Moon, Jang;Park, Jun-Mo;Kong, Gil-Young
    • Journal of Navigation and Port Research
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    • v.41 no.3
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    • pp.79-86
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    • 2017
  • Ballast water filled into and discharged from the ballast tank of a ship has a negative impact on local marine environment due to various aquatic organisms contained therein. The IMO developed and adopted "The International Convention for the Control and Management of Ships Ballast Water and Sediments, 2004" with the purpose of protecting the marine environment from transfer of harmful aquatic organisms in ballast water carried by ships. The IMO BWM Convention was approved in September 2016 and ships must be equipped with ballast water management system after September 2017. Ships' ballast water treatment methods are divided into using active substances as electrolytic type, ozone type, chemical dosing type and using physical treatment type as filter type, ultraviolet type. It is also used with a combination of two methods. Electrolysis is superior in terms of cost and efficiency. In this study, basic principles, components, and land base test contents of electrolysis ballast water treatment system, a direct electrolyzed ballast water treatment system, were examined. Land base test was conducted with 300m3/h capacity device at the KIOST Geoje plant where the government test facility was installed. This test validated that the system meets IMO standards.

Pharmacokinetic Study of YH1885 (I): Absorption, Distribution and Excretion of $^{14)C-YH1885$ in Rats (YH1885의 체내동태(제1보):흰쥐에서 $^{14)C-YH1885$의 단회투여시 흡수, 조직분포 및 배설)

  • Ahn, Byung-Nak;Fujio, Naoki;Kusumoto, Naotoshi;Abe, Yoshifumi;Odomi, Masaaki;Lee, Jong-Wook
    • YAKHAK HOEJI
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    • v.41 no.3
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    • pp.335-344
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    • 1997
  • The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.

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Development of Site Classification System and Modification of Design Response Spectra considering Geotechnical Site Characteristics in Korea (I) - Problem Statements of the Current Seismic Design Code (국내 지반특성에 적합한 지반분류 방법 및 설계응답스펙트럼 개선에 대한 연구 (I) - 국내 내진설계기준의 문제점 분석)

  • Yoon, Jong-Ku;Kim, Dong-Soo;Bang, Eun-Seok
    • Journal of the Earthquake Engineering Society of Korea
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    • v.10 no.2 s.48
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    • pp.39-50
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    • 2006
  • Site response analyses were peformed based on equivalent linear technique using the shear wave velocity profiles of 162 sites collected around the Korean Peninsula. The she characteristics, particularly the shear wave velocities and the depth to bedrock, are compared to those in the western United States. The site coefficients of short period $(F_a)$ and the long period $(F_v)$ obtained from this study were significantly different compared to 1997 Uniform Building Code (1997 UBC). $F_a$ underestimated the motion in shot period ranges and $F_v$ overestimated the motion in mid period ranges in Korean seismic guideline. It is found that the existing Korean seismic design code were is required to be modified considering geological site conditions in Korea for the reliable estimation of sue amplification. Problems of the current seismic design code were dicussed in this paper and the development of site classification method and modification of desing response spectra were discussed in the companion papers(II-Development of Site Classification System and III-Modification of Dosing Response Specra).