• Title/Summary/Keyword: Half Life Time

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Interspecies Scaling of Roxithromycin Pharmacokinetics Across Species (록시스로마이신의 체내동태에 대한 이종간 예측모델)

  • Lim, Jong-Hwan;Park, Byung-Kwon;Yun, Hyo-In
    • Journal of Veterinary Clinics
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    • v.24 no.1
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    • pp.5-9
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    • 2007
  • The purpose of this study was to examine the allometric analysis of roxithromycin using pharmacokinetic data. The pharmacokinetic parameters used were $half-life(t_{1/2})$, mean residence time (MRT), clearance (Cl) and volume of distribution at steady state $(V_{ss})$. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula $Y=aW^b$, where 'Y' is $t_{1/2}$, MRT, Cl, or $V_{ss}$, W the body weight and 'a' is an allometric coefficient (intercept) that is constant for a given drug. The exponential term, 'b', is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. As results of the allometric analyses, the logarithms of $t_{1/2}$, MRT, Cl, and $V_{ss}$ were linearly related to the logarithms of body weight. Results of the current analyses could provide information on appropriate doses of roxithromycin for all species.

Can denosumab be a substitute, competitor, or complement to bisphosphonates?

  • Kim, Su Young;Ok, Hwoe Gyeong;Birkenmaier, Christof;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • v.30 no.2
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    • pp.86-92
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    • 2017
  • Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption. Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of resorption performed by activated osteoclasts, are still the drugs of choice to prevent and treat osteoporosis. The merits of denosumab are reversibility targeting the RANKL, lack of adverse gastrointestinal events, improved adherence due to convenient biannual subcutaneous administration, and potential use with impaired renal function. The known adverse reactions are musculoskeletal pain, increased infections with adverse dermatologic reactions, osteonecrosis of the jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3 days, with maximum reduction occurring by 1 month. The mean time to maximum denosumab concentration is 10 days with a mean half-life of 25.4 days. In conclusion, the convenient biannual subcutaneous administration of 60 mg of denosumab can be considered as a first-line treatment for osteoporosis in cases of low compliance with BPs due to gastrointestinal trouble and impaired renal function.

HPLC Determination and Pharmacokinetics of Endogenous Acetyl-L-Carnitine (ALC) in Human Volunteers Orally Administered a Single Dose of ALC

  • Kwon, Oh-Seung;Chung, Youn-Bok
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.676-681
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    • 2004
  • Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}/mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

Effect of Stabilizers on Performance of Electroluminescence Display Device (안정화제가 무기 전계발광 디스플레이 소자 성능에 미치는 영향)

  • Shin, DongHyuk;Lim, JongChoo
    • Korean Chemical Engineering Research
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    • v.45 no.4
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    • pp.356-363
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    • 2007
  • The stability of paste solutions for electroluminescence display(ELD) device was found to be greatly affected by kind and dosage of a stabilizer used. The stabilizer Disperbyk-180 showed the best stability performance against phosphor paste solutions among the stabilizers used during this study. The phosphor paste solutions remained stable over 90 days with a wide range of added amounts of Disperbyk-180. Based on the above results, screen printing test was performed. The addition of Disperbyk-180 into phosphor and dielectric paste solutions produced improved qualities such as no phase separation, no bubble generation and no significant viscosity change during printing process. Especially for the phosphor paste solution, both uniformity and brightness were significantly improved and the excellent adhesion onto the ITO film was found. The ELD device fabricated using the above same paste solutions showed brightness of $57.6cd/m^2$ at 100V and 400 Hz. The half lifetime of ELD device was measured as 1,250 hours and almost the same value observed with imported commercial paste solutions.

Toxicokinetic Modeling of Ethyl Paraben Administered Orally in Rats (랫드에 경구투여한 에틸파라벤의 독물동력학 모델링)

  • Kim, PanGyi
    • Journal of Environmental Health Sciences
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    • v.40 no.5
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    • pp.407-412
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    • 2014
  • Objectives: The internal dose of ethyl parabens is important in order to evaluate the risk of this chemical. However, there are little PK model data for parabens to apply this. This experiment attempted PK modeling to ascertain PK values. Methods: Twenty mg/kg ethyl paraben was administered orally to Sprague-Dawley rats at the same point in time. The rats were sacrificed at times 0, 15, 30 and minutes, and 1, 2, 4, 8, 12, 24 hours after oral gavage. Blood and urine were collected and pretreated for analysis. Accuracy, precision and LOD (limit of detection) were calculated for this analysis. Ethyl paraben, detected by HPLC-MS, was applied to PK modeling using Berkeley Madonna. Results: This study showed 100.1-103.7% accuracy, 1.4-3.7% precision and a 1.0 ng/mL limit of detection. Orally administered ethyl paraben reached maximum concentration after 30 minutes of dosing in serum and urine of rats. The concentrations were 2,354 ng/mL in serum and 386,000 ng/mL in urine samples. These peak concentrations were excreted after one hour of intubation over 12 hours. For the pharmacokinetic parameters of ethyl paraben revealed using Berkeley Madonna, the absorption rate was 5.539/hour, the excretion rate was 0.048/hour, the half-life was 14.441 hours and AUC was 481,186 ng hour/mL. Conclusion: Orally administered ethyl paraben was absorbed rapidly in rats and excreted in urine. This chemical, ethyl paraben, accumulated in the body but was excreted over 12 hours after dosing.

Evaluation of structural safety reduction due to water penetration into a major structural crack in a large concrete project

  • Zhang, Xiangyang;Bayat, Vahid;Koopialipoor, Mohammadreza;Armaghani, Danial Jahed;Yong, Weixun;Zhou, Jian
    • Smart Structures and Systems
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    • v.26 no.3
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    • pp.319-329
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    • 2020
  • Structural damage to an arch dam is often of major concern and must be evaluated for probable rehabilitation to ensure safe, regular, normal operation. This evaluation is crucial to prevent any catastrophic or failure consequences for the life time of the dam. If specific major damage such as a large crack occurs to the dam body, the assessments will be necessary to determine the current level of safety and predict the resistance of the structure to various future loading such as earthquakes, etc. This study investigates the behavior of an arch dam cracked due to water pressure. Safety factors (SFs), of shear and compressive tractions were calculated at the surfaces of the contraction joints and the cracks. The results indicated that for cracking with an extension depth of half the thickness of the dam body, for both cases of penetration and non-penetration of water load into the cracks, SFs only slightly reduces. However, in case of increasing the depth of crack extension into the entire thickness of the dam body, the friction angle of the cracked surface is crucial; however, if it reduces, the normal loading SFs of stresses and joints tractions reduce significantly.

Effect of Chronic Treatment of Ginseng Extract on the Clearance of Blood Carbon Monoxide in Rat (인삼추출물의 장기적인 급여가 흰쥐의 혈중 CO-Hb 제거에 미치는 영향)

  • Lee, Young-Gu;Sohn, Hyung-Ok;Lim, Heung-Bin;Lee, Dong-Wook
    • Journal of Ginseng Research
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    • v.19 no.3
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    • pp.225-230
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    • 1995
  • The effect of long-term ginseng (Panax ginseng C.A. Meyer) administration on the clearance of carboxyhemoglobin (CO-Hb) and the property of blood gases was investigated in rats. Rats were received ginseng water extract (0.025% in drinking water) for 42 weeks starting at the age of 6 weeks. They were exposed to the diluted mainstream smoke generated from 15 filter cigarettes for 20 min in a round polycarbonate chamber (D37 cmXH13 cm). Under this condition, the mean CO-Hb content of control and the ginseng-treated rats immediately after the exposure was nearly the same as 13.8$\pm$2.9 f) and 13.9$\pm$1.6%, respectively. However, CO-Hb was more rapidly removed from blood in the ginseng treated rats than in untreatEd control with the laps of time, namely, its biological half life In the former was 36.9$\pm$1.5 min and in the latter was 56.9$\pm$13.2 min. Although long-term ginseng treatment did not affect the content of hemoglobin and blood pH of rats, it slightly increased blood oxygen content and its partial pressure value, and decreased levels of carbon dioxide and bicarbonate. These results suggest that long-term administration of rats with ginseng extract accelerate the elimination of CO from the blood. This effect seems to be related to the enhancement of oxygen consumption of the rat by a certain action of ginseng components as previously reported.

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LIMITED OXIDATION OF IRRADIATED GRAPHITE WASTE TO REMOVE SURFACE CARBON-14

  • Smith, Tara E.;Mccrory, Shilo;Dunzik-Gougar, Mary Lou
    • Nuclear Engineering and Technology
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    • v.45 no.2
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    • pp.211-218
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    • 2013
  • Large quantities of irradiated graphite waste from graphite-moderated nuclear reactors exist and are expected to increase in the case of High Temperature Reactor (HTR) deployment [1,2]. This situation indicates the need for a graphite waste management strategy. Of greatest concern for long-term disposal of irradiated graphite is carbon-14 ($^{14}C$), with a half-life of 5730 years. Fachinger et al. [2] have demonstrated that thermal treatment of irradiated graphite removes a significant fraction of the $^{14}C$, which tends to be concentrated on the graphite surface. During thermal treatment, graphite surface carbon atoms interact with naturally adsorbed oxygen complexes to create $CO_x$ gases, i.e. "gasify" graphite. The effectiveness of this process is highly dependent on the availability of adsorbed oxygen compounds. The quantity and form of adsorbed oxygen complexes in pre- and post-irradiated graphite were studied using Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and Xray Photoelectron Spectroscopy (XPS) in an effort to better understand the gasification process and to apply that understanding to process optimization. Adsorbed oxygen fragments were detected on both irradiated and unirradiated graphite; however, carbon-oxygen bonds were identified only on the irradiated material. This difference is likely due to a large number of carbon active sites associated with the higher lattice disorder resulting from irradiation. Results of XPS analysis also indicated the potential bonding structures of the oxygen fragments removed during surface impingement. Ester- and carboxyl-like structures were predominant among the identified oxygen-containing fragments. The indicated structures are consistent with those characterized by Fanning and Vannice [3] and later incorporated into an oxidation kinetics model by El-Genk and Tournier [4]. Based on the predicted desorption mechanisms of carbon oxides from the identified compounds, it is expected that a majority of the graphite should gasify as carbon monoxide (CO) rather than carbon dioxide ($CO_2$). Therefore, to optimize the efficiency of thermal treatment the graphite should be heated to temperatures above the surface decomposition temperature increasing the evolution of CO [4].

Characteristics of land-use and population change in rural area by developing new expressway - A case study on Chungbu expressway and its surrounding areas in the south of Kyuinggi province - (고속도로 개발 전후의 농촌지역 토지이용 및 인구변화 특성 - 경기도 남부 중부고속도로와 주변지역을 중심으로 -)

  • Kim, Dae-Sik
    • Journal of Korean Society of Rural Planning
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    • v.9 no.2 s.19
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    • pp.49-55
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    • 2003
  • The purpose of this study is to analyze the impact of land-use and population change in rural area by new expressway. Chungbu expressway constructed in 1987, going through the south area of Kyunggi province from Seoul, was selected as a case expressway, and also 2 cities and 18 subdivisions of county in its surrounding area, as a case study area. To analyze the change characteristics before and after the construction, land-use maps of 1986 and 1996 were collected, including the census data for the years in cities and counties yearbooks. Remote sensing technology was applied to classify the land-use maps with six types of land use. Geographic information system was also used for spatial analysis, such as the land-use and accessibility changes. A 5 km buffer zone from interchange of the expressway showed about two times increase of urbanized built-up area than a 5 km buffer zone from the expressway. Accessibility from Seoul and cities was improved in most areas, which is accessing to Seoul through existing Youngdong expressway. Ten rural areas showed increased population with accessibility of average 52 minutes to Seoul and 19 minutes to cities, while eight areas showed decreased population with average 73 minutes to Seoul and 35 minutes to cities. This shows that the threshold value, which is time distance to Seoul and cities for population increase or decrease, one and half hours, respectively. Urbanized area was increased in most areas, even in population decrease areas, so this indicates that there are thinning rural areas, increasing urbanized area while decreasing population.

Effects of Hydrocortisone on the Pharmacokinetics of Loratadine after Oral and Intravenous Loratadine Administration to Rats

  • Choi, Jun-Shik;Choi, In;Burm, Jin-Pil
    • Biomolecules & Therapeutics
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    • v.17 no.2
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    • pp.205-210
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    • 2009
  • The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.