• Title/Summary/Keyword: Half-life(t1/2)

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Pharmacokinetics and Pharmacodynamics Following Oral Administration of Pimobendan-Pentoxifylline Powder Formulation Mixture in Dogs (개에서 피모벤단-펜톡시필린 분말 제형 합제의 경구투여시 약물약동학 및 약물약력학에 대한 연구)

  • Ro, Woong-bin;Song, Doo-won;Kang, Yeo-lim;Park, You-jin;Yoo, Cho-rong;Lee, Jong-ho;Kim, Ki-hun;Jeong, Sang-hee;Kang, Min-hee
    • Journal of Veterinary Clinics
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    • v.36 no.1
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    • pp.46-52
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    • 2019
  • Pimobendan has inotropic and vasodilating effects on cardiovascular system, and pentoxifylline is known to decrease blood viscosity and improve blood flow to the heart. This study investigated the pharmacokinetics and pharmacodynamics following oral administration of pimobendan-pentoxifylline powder mixture in dogs. Eight healthy dogs were included and were divided into control (n = 4) and experimental (n = 4) groups. Vehicle powder and pimobendan-pentoxifylline powder mixture (pimobendane 0.25 mg/kg, pentoxifylline 15 mg/kg) were administrated orally to control and experimental groups, respectively. Plasma samples and measurement of echocardiographic indices were obtained for 24 hours following administration. Pimobendan and pentoxifylline concentrations were investigated using liquid chromatography-mass spectrometer (LC-MS) assay. The elimination half-life ($T_{1/2}$) were $2.65{\pm}1.42hours$ for pimobendan and $0.29{\pm}0.23hours$ for pentoxifylline. The time to reach maximum concentration ($T_{max}$) were $1.08{\pm}0.72hours$ for pimobendan and $0.29{\pm}0.14hours$ for pentoxifylline. The maximum blood concentration ($C_{max}$) were $2.83{\pm}1.50ng/mL$ for pimobendan and $1184.33{\pm}932.37ng/mL$ for pentoxifylline. Among echocardiographic indices, fractional shortening (FS), left ventricular internal diameter at end systole (LVIDs), and pre-ejection period (PEP) showed significant changes at 1-4 hours after the administration of pimobendan-pentoxifylline powder mixture. No adverse effects were observed during the investigation. This study demonstrates that pimobendan-pentoxifylline powder mixture can be used to control cardiovascular diseases in dogs.

HPLC Analysis of Piroxicam in the Rabbit Plasma and its Bioavailability after the Transdermal Administration of Patches (토끼 혈장 중 피록시캄의 HPLC 분석 및 패취제 투여 후 경피흡수)

  • Shin, Dae-Hwan;Park, Seong-Hyeok;Lee, Gyeong-Bok;Lee, Chong-Kil;Chung, Youn-Bok
    • Journal of Pharmaceutical Investigation
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    • v.39 no.3
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    • pp.177-183
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    • 2009
  • A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of piroxicam in the rabbit plasma. After a treatment of plasma sample by liquid-liquid extraction, the drug was analyzed on an HPLC system with ultraviolet detection at 330 nm. HPLC was carried out using reversed-phase isocratic elution with a C18 column, a mobile phase of a mixture of acetonitril, doubly deionized water and acetic acid 43.74:56.00:0.26 v/v%) at a flow rate of 1.1 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma sample was linear over the concentration range of 0.01-2.0 ${\mu}$g/mL. The intra- and inter-day assay accuracies of this method ranged from 86.82% to 108.33% of normal values and the precision did not exceed 13% of relative standard deviation. The plasma concentration of piroxicam decreased to below the quantifiable limit at 12 hr after the i.v. bolus administration to rabbits following dose of 0.375 mg/kg yielding a apparen t plasma half life of 1.38 hr. The transdermal route prolongs plasma levels of piroxicam. The bioavailability, calculated from the dose-adjusted ratio of the $AUC_{transdermal}$ to the $AUC_{i.v.}$, was 7.44%. The plasma concentration of piroxicam was detected by 48 hr after the transdermal administration of patch at a dose of 32 mg/kg. This method was suitable for cutaneous absorption studies of piroxicam in the rabbit after transdermal administration of different types of dosages of the drug.

Development and Characterization of Hyperglycosylated Recombinant Human Erythropoietin (HGEPO)

  • JarGal, Naidansuren;Min, Kwan-Sik
    • Reproductive and Developmental Biology
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    • v.33 no.2
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    • pp.77-83
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    • 2009
  • Erythropoietin (EPO), a glycoprotein hormone produced from primarily cells of the peritubular capillary endothelium of the kidney, is responsible for the regulation of red blood cell production. We have been investigating the roles of glycosylation site added in the biosynthesis and function of recombinant protein. We constructed three EPO mutants ($\Delta$69, $\Delta$105 and $\Delta$69,105), containing an additional oligosaccharide chains. EPOWT and EPO$\Delta$69 were effectively expressed in transient and stably transfected CHO-K1 cell lines. But, it wasn't detected any protein in the culture medium of EPO$\Delta$105 and EPO$\Delta$69,105 mutants. The growth and differentiation of EPO-dependent human leukemic cell line (F36E) were used to measure the cytokine dependency and in vitro bioactivity of rec-hEPO. MTT assay values were increased by survival of F36E cells at 24h. To analysis biological activity in vivo, two groups of ICR-mice (7 weeks old) were injected subcutaneously with 10 IU per mice of rec-hEPO molecules on days 0 and 2. Red blood cell and hematocrit values were measured on 6 days after the first injection. The hematocrit values were remarkably increased in all treatment groups. The pharmacokinetic analysis was also affected in the mice injected with rec-hEPO molecules 2.5 IU by tail intravenous. Protein samples were detected by Western blotting. An EPO$\Delta$69 protein migrated as a broad band with an average apparent molecular and detected slightly high band. Enzymatic N-deglycosylation resulted in narrow band and was the same molecular size. The biological activity of EPO$\Delta$69 was enhanced to compare with wt-hEPO. The half-life was longer than wt-hEPO. The results suggest that hyperglycosyalted recombinant human erythropoietin (EPO$\Delta$69) may have important biological and therapeutic good points.

Removal Characteristics of Synthetic Musk Compounds in Water by Ozone Treatment (오존처리에 의한 수중의 인공 사향물질 제거특성)

  • Seo, Chang-Dong;Son, Hee-Jong;Yoom, Hoon-Sik;Lee, Sang-Won;Ryu, Dong-Chun
    • Journal of Korean Society of Environmental Engineers
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    • v.34 no.2
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    • pp.73-78
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    • 2012
  • In this study, three different synthetic musk compounds (SMCs) in the Nakdong river water (raw water) and rapid sand filtered water were treated by $O_3$ process. The experimental results showed that the removal efficiency of musk ketone (MK) was lower than removal efficiency of AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) and HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[c]-2-benzopyran) for both the raw water and the rapid sand filtered water. And in general, the removal efficiencies of three SMCs in the raw water were lower than that in the sand filtered water. Under the $O_3$ dose of 0.5~10.0 mg/L, the removal rate constants (k) of three SMCs for the raw and sand filtered waters increased rapidly with the increased $O_3$ dose. In the case of drinking water treatment plants (DWTPs) which were selected pre- and post-$O_3$ processes (located in the downstream of Nakdong River), operation conditions of pre- and post-$O_3$ process were $0.5{\sim}2.0mg{\cdot}O_3/L$ (2~4 min) and $0.5{\sim}2.5mg{\cdot}O_3/L$ (6~8 min). Therefore, $O_3$ doses and contact times of same conditions with above were very difficult to remove SMCs in DWTPs.

A Suggestion for Counting Efficiency Management of the Automation Instrument (자동화장비 계측효율 관리적 측정방법 제안)

  • Park, Jun Mo;Kim, Han Chul;Choi, Seung Won
    • The Korean Journal of Nuclear Medicine Technology
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    • v.22 no.2
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    • pp.105-111
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    • 2018
  • Purpose Quality control of instrument takes up a large part in the Radioimmunoassays. The gamma-ray instrument, which is one of the important instruments in the laboratory, observes the condition and performance of instrument and performs quality control of the instrument by measuring the Normalization, Calibration, Background and etc. However, there are some automation instruments which can't measure the counting efficiency of gamma-ray meters, resulting in insufficient management in terms of performance evaluation of gamma-ray meters. Therefore, the purpose of this paper is to manage the quality control continuously and regularly by suggesting how to measure the counting efficiency of gamma-ray instruments. Materials and Methods In case of a comparative measurement method to a gamma-ray instrument dedicated to nuclear medical examination, the CPM and counting efficiency can be obtained after the measurement of normalization by inserting the I-125 $200{\mu}L$(CPM 50,000~500,000) into the test tube. With this CPM and counting efficiency values, it's possible to calculate the measurement of the DPM value and count the CPM from the automation instrument from the same source, and enter the DPM to calculate the counting efficiency using a comparative measurement method. Another method is to calculate the counting efficiency by estimating the half life using the radiation source information of the tracer in B test reagents of company A. Results According to the calculation formula using the DPM obtained by counting the normalization of gamma-ray meters, the detection efficiency was 75.16% for Detector 1, 76.88% for Detector 2, 77.13% for Detector 3, 75.36% for Detector 4 and 73.2% for Detector 5 respectively. Using another calculation formula estimated from the shelf life, the data of the detection efficiency from Detector 1 to Detector 5 were 74.9%, 75.1%, 76.5%, 74.9% and 73.2% respectively. Conclusion Although the accuracy of counting efficiencies of both methods are insufficient, this is considered to be useful for ongoing management of quality control if counting efficiency is managed after setting the acceptable ranges. For example, if the measurement efficiency is set to 70% or higher, the allowed %difference between measurements is within 3% and the %difference with the detector wall is set within 5%.

Study on Physicochemical Properties of Pesticides. (II) Water Solubility, Hydrolysis, Vapor Pressure, and Octanol/water Partition Coefficient of Flupyrazofos (농약의 물리화학적 특성 연구 (II) Flupyrazofos의 수용성, 가수분해, 증기압, 옥탄올/물 분배계수)

  • Kim, Jeong-Han;Kim, Yong-Hwa;Kim, Kyun
    • Applied Biological Chemistry
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    • v.40 no.1
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    • pp.76-79
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    • 1997
  • Several physicochemical properties such as water solubility, vapor pressure, hydrolysis and octanol/water partition coefficient(Kow) of flupyrazofos, the first organophosphorus insecticide developed in Korea, were measured based on EPA and OECD methods. Water solubility was low showing 0.80 ppm at $25^{\circ}C$ and in hydrolysis study, half-life at $25^{\circ}C$ was 266.5 hr(pH 4.0), 180.0 hr(pH 7.0) and 120.9 hr(pH 9.0) demonstrating instability in alkaline solution. At $40^{\circ}C$ hydrolysis rate was $2{\sim}4$ times higher than that at $25^{\circ}C$. The equation log P=0.673-(1565.4/T) was obtained from vapor pressure experiments at three different temperatures (25, 35, $45^{\circ}C$) and $2.81{\times}10^{-5}$ torr was obtained at $25^{\circ}C$. This value is similar to that of diazinon and 1,000 times lower than that of DDVP suggesting it would not give environmental contamination by volatilization. High log Kow(5.24) was observed and this might result in bioconcentration through food chain. However, its possibility is not likely to be high due to its relatively rapid hydrolysis.

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The Influence of Stress on Smoking and Drinking of High School Students (스트레스가 고등학생의 흡연.음주에 미치는 영향)

  • Kim, Jong-Mun;Park, Young-Soo
    • The Journal of Korean Society for School & Community Health Education
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    • v.3
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    • pp.35-58
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    • 2002
  • This research attempted to investigate the real state of adolescent smoking and drinking, and to study how stress influences on smoking and drinking of high school students. This data was collected from 837 first and second grade students in a vocational high school in Go-yang city, Gyeonggi province. Data analysis consisted of frequency, percentage, Chi-square, T-test, step-wise regression analysis, using SPSSWIN. The results of analysis were as follows: First, 51.7% of the students have never smoked, while 48.3% have experienced smoking. Most students started smoking in the second year of the middle school, though 17.6% of the smokers already started in the elementary school. The strongest motive of initial smoking was curiosity, next the inducement of friends, and 10.9% of them smoked to get rid of stress. Their favorite place for smoking was in the order of the entertainment centers, schools, and private academies. They personally purchased cigarettes mostly at the store. Most of them smoked less than 5 cigarettes a day, but 3.7% smoked more than a pack of cigarettes a day, usually with friends rather than alone. Second, the ratio of drinking was relatively high 78.1%, and their initial drinking experience was most frequent at the third year of the middle school. The initial motive of drinking was mostly curiosity and the inducement of friends, but 10.7% of them started drinking to reduce stress and anxiety. The places for buying alcohol and drinking were bars or restaurants. The ratio of habitual drinking was 45.1%, and the ratio of irregular drinking was 53.3%. 1.8% of the drinking students enjoyed drinking everyday. The amount of drinking varied from half a bottle to two bottles of Soju, and the drinking problem was serious to see that 11% of them drank more than two bottles at a time. Because 84.4% drank in groups with friends, a thorough and systematic supervision and education of the peer group drinking is essential. Third, as for the relationship between personal matters and smoking, it was found that there was a positive relation between smoking and sex, but there was no correlation between smoking and school years. Adolescent smoking was also related with scholastic achievement, the number of friends, and the existence of parents. Fourth, as for the relationship between personal matters and drinking, it was found that there was no correlation between drinking and sex, but there was a positive relation between drinking and school years. Fifth, the average index of stress was students themselves(2.58), school life(2.53), family life(2.19), friends(2.00), and the total index of stress was 2.33. Sixth, there appeared a marginal negative correlation between stress and 'drinking and smoking' in Pearson coefficient of correlation r to see the influence of stress on smoking and drinking. The difference of the average index of stress according to smoking and drinking bears meaningful difference for all students, smokers and non-smokers, drinkers and abstainers in students themselves, school life, family life, friends, and total stress. Smoking has an effect on family life most, school life next, and drinking has an effect on school life most, family life next, with the explanation power of 11% and 9% respectively, in a regression analysis to analyze the factors influencing on smoking and drinking among the factors of stress.

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Pharmacokinetics of a New Histone Hl Protein (p961), an Arthritis-suppressing Agent, in Rats and Rabbits (항류마치스 효과를 갖는 새로운 히스톤 H1 단백질 (p961)의 흰쥐와 토끼에 대한 약물동태)

  • 우수경;윤민혁;이재흥;권광일
    • YAKHAK HOEJI
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    • v.45 no.4
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    • pp.378-386
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    • 2001
  • A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....

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Pharmacokinetic Interaction between Diltiazem and Paclitaxel in Rats (딜티아젬과 파크리탁셀의 약물동태학적 상호작용)

  • Choi, Jun-Shik;Kim, Hyung-Joong
    • Journal of Pharmaceutical Investigation
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    • v.33 no.4
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    • pp.299-304
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    • 2003
  • The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

A Study on the Well-being Related Awareness and Dietary Life Pattern in Urban Housewives (도시 주부들의 웰빙에 대한 인식과 식생활유형에 대한 연구)

  • Park, Young-Sim;Myung, Choon-Ok;Lee, Ki-Wan;Nam, Hae-Won
    • Journal of the Korean Society of Food Culture
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    • v.20 no.5
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    • pp.574-583
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    • 2005
  • To investigate the importance and practice of well-being related dietary life pattern such as purchasing food materials, food habits and eating out, a survey was conducted by questionnaire and 5-point Likert score in Seoul and Gyeonggi-Do, September, 2004 and April, 2005. The responses of 732 housewives who were over 40 years were analyzed by SPSS package program. The results were as follows. Most of them were 40-49 years(74.4%), graduated highschool (66.6%) and their family type was nuclear family type(81.4%). Almost half of them had full-time job (37.1%) and part time job (15.4%). The average importance score of 'food habits', 'purchasing food materials' and 'eating out' were $4.15{\pm}0.91,\;4.06{\pm}0.96\;and\;3.25{\pm}1.01$ respectively. But the average practice score of 'food habits' was greater($3.58{\pm}1.06$) than 'purchasing food materials ($3.19{\pm}1.19$)' and 'eating out($2.54{\pm}1.05$)'. Among 5 types of 'food habits', the type of 'cut down on eating fast food' had the greatest score of importances ($4.31{\pm}0.97$) but the difference between importance and practice was greatest(0.94). Also 'consume home-made food rather than processed or ready to food' showed great scores in importance ($4.28{\pm}0.87$) and practice($3.87{\pm}1.04$). 'Consume fruits and vegetables rather than meats' and 'avoid heavy use of oils' had the importance score of $4.04{\sim}4.19$. But the practice score of 'avoid heavy use of oils' was the lowest($3.39{\pm}0.97$). Among four types of purchasing of food materials, 'purchase domestic agricultural food' was greatest($4.37{\pm}0.78$) and 'don't purchase genetically modified food' 'purchase organic food' and 'purchase whole grain products' were also great ($3.92{\sim}3.99$). But the practice score of 'purchase organic/low chemical foods($2.77{\pm}0.98$)' and 'don't purchase genetically modified food($2.99{\pm}1.41$)' were lowest. 'Go to well being restaurant' in three types of 'eating out' showed greatest in importance($3.35{\pm}0.96$) but the practice score($2.47{\pm}0.10$) was lower than the importance score. Also 'choose menu with comparing calories' had the lower score in practice($2.45{\pm}1.06$) rather than importance score($3.22{\pm}1.03$). In regarding to 'food habits', the importance score were significantly affected by type of food expense (p<0.05) and health status (p<0.05). The importance score of 'purchase food materials' were significantly affected by the type of food expense (p<0.001), type of residence(p<0.05), and self assessment of weight(p<0.05). Monthly income, especially more 400 million won, was the commonly significant effector in practice score of 'purchase food materials' and 'eating out'.