• Title/Summary/Keyword: 약동

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Validation of the LC-MS/MS Method for Ginsenoside Rb1 Analysis in Human Plasma (LC-MS/MS를 이용한 인체 혈장에서 Ginsenoside Rb1의 분석법 검증)

  • Han, Song-Hee;Kim, Yunjeong;Jeon, Ji-Young;Hwang, Minho;Im, Yong-Jin;Lee, Sun Young;Chae, Soo-Wan;Kim, Min-Gul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.12
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    • pp.1753-1757
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    • 2012
  • A new liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of ginsenoside Rb1 in human plasma was developed and validated. The separation was performed on a Agilent C18 column ($4.6mm{\times}150mm$, particle size 5 ${\mu}m$) with a gradient elution of 0.1% formic acid in water and 0.1% formic acid in methanol and a flow rate of 0.9 mL/min. The analyte was determined using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode (m/z 1131.714${\rightarrow}$365.303). Human plasma samples were extracted with acetone : water (50:50) by the liquid-liquid extraction method. The method was linear over the dynamic range of 10~500 ng/mL with a correlation coefficient of r=0.9995. The intra-and inter-day precision over the concentration range of ginsenoside Rb1 was lower than 5.8% (correlation of variance, CV), and the accuracy was between 96.0~104.6%. This LC-MS/MS assay of ginsenoside Rb1 in human plasma is applicable for quantification in a pharmacokinetic study.

Pharmacokinetic/Pharmacodynamic Analysis of Metoprolol in Dogs (실험견에서 Metoprolol 약리효과의 약동/력학적 검토)

  • Oh, Dong-Jin;Jang, In-Jin;Lee, Kyung-Hun;Yim, Dong-Seok;Kim, Hyung-Kee;Shin, Sang-Goo;Park, Chan-Woong;Shin, Jae-Gook
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.251-259
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    • 1995
  • Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

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Whitehead's Concept of Proposition and Creative Advance of Nature (화이트헤드의 명제론 연구 - 화이트헤드의 명제론과 현실의 창조적 전진 -)

  • Chun, Chul
    • Journal of Korean Philosophical Society
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    • v.116
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    • pp.351-370
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    • 2010
  • Whitehead's metaphysics and philosophy of nature rest on his awareness of the metaphysical problem of the relation between "I", the "creative advance" and forces of the universe. Whitehead attempted to systematize human experience of the world based on logical explorations. In this context it is important to note that his discussion of proposition and language is closely connected with his works on a systematic theory of nature. Whitehead proposes a metaphysical concept of proposition also based on the creative advance of the universe. His theory of proposition is designed to show that human language is constructions of the relations between logical and real events in the creative universe which refer to a particular point of view. In this view, a variety of verbal possibilities in the multiple worlds can be realized in the same proposition. For Whitehead the emergence of novelty in the function of proposition is an essential property of the creative universe. This paper will try to give a discussion to Whitehead's theory of proposition with regard to the emergence of nature. Especially I emphasize in this paper Whitehead's idea and meaning of proposition for the development of the creative advance of nature as one aspect of particular importance.

Nietzsche in the Square of Carlos Alberto (카를로스 알베르토 광장의 니체)

  • Lee, Wang-joo
    • Journal of Korean Philosophical Society
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    • v.142
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    • pp.221-241
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    • 2017
  • I try to elucidate the essence of cinematic art in terms of Nietzsche's physiological philosophy of art. According to Nietzsche, the mise-en-$sc{\grave{e}}nes$ in the film are expressions of willingness to the power of the author, the director. These are not re-imitations of the imitations with Platonic measure, sinker, number, but framing the elan vital Erde, die $urspr{\ddot{u}}ngliche$ Vorstellung with the director's body-camera. In this context, the film is essentially die Kunst des Lebens, in which the body and the earth are mediated by cameras. Therefore, it is not the eyes or the head, but the body that is necessary to appreciate film art. But the body at this time does not mean the heavy body of Hollywood standard audiences manipulated, controlled, or transformed by capital. We should stand in front of the film work with body shaking between trauma and Rausch, a dancing body, and a light and fresh body. Only by watching film with the body, can we achieve the small revolutions in everyday life. For example, if we watch $B{\acute{e}}la$ Tarr's film The Turin Horse in such a way, we can no longer be the dwarfed human beings, der Herde-Mensch. Also, $B{\acute{e}}la$ Tarr's mise-en-scene will make us realize why Nietzsche had said that there is art to us not to be destroyed by the platonic truth.

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.

Biological Roles of the Glycan in the Investigation of the Novel Disease Diagnosis and Treatment Methods (신개념 질병 진단 및 치료 연구에 있어서의 당사슬의 생물학적 역할)

  • Kim, Dong-Chan
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1379-1385
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    • 2018
  • Glycans are attached to proteins as in glycoproteins and proteoglycans. They are found on the exterior surface of cells. O- and N-linked glycans are very common in eukaryotic cells but may also be found in prokaryotes. The interaction of cell surface glycans with complementary glycan binding proteins located on neighboring cells, other cell types, pathogens like virus, or bacteria is crucial in biologically and biomedically important processes like pathogen recognition, cell migration, cell-cell adhesion, development, and infection. Their implication in pathological condition, suggests an important role for glycans as disease markers. In addition, a great amount of research has been shown that appropriate glycosylation of a recombinant therapeutic protein is critical for product solubility, stability, pharmacokinetics and pharmacodynamics, bioactivity, and safety. Besides, cancer-associated glycosylation changes often involve sialic acid in glycan branch which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the glycan's biological function and describing the relevance among the glycosylation, disease diagnosis and treatment methods. Furthermore, the high-throughput analytic methods available to measure the profile changing patterns of glycan in the blood serum as well as possible underlying biochemical mechanisms.

Residue level and pharmacokinetics of trichlorfon in the Japanese eel (Anguilla japonica) after bath treatment (Trichlorfon (TCF)의 약욕 투여에 따른 뱀장어 체내 약물 잔류량 및 약물동태학 연구)

  • Jo, Hyun Ho;Chung, Joon Ki
    • Journal of fish pathology
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    • v.35 no.1
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    • pp.93-102
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    • 2022
  • This study performed a trichlorfon (TCF) residue and pharmacokinetic analysis with Japanese eels, Anguilla japonica, to obtain baseline data to establish the maximum residue level (MRL) of TCF in A. japonica. After dipping A. japonica in 30 ppm and 150 ppm of TCF at 28℃ and 18℃, drug residue in the body was analyzed with LC-MS/MS, and these results were further analyzed with the PK solver program to obtain the pharmacokinetic parameters of TCF in the serum, muscles, and liver. The maximum concentrations (Cmax) in the serum, muscles, and liver were 25.87-357.42, 129.91-1043.73, and 40.47-375.20, respectively, and the time to maximum concentration (Tmax) was 0.13-1.32h, 1.17-3.34h, and 0.14-5.40h, respectively. The terminal elimination half-life (T1/2) was 2.13-3.92h, 5.30-10.35h, and 0.65-13.81h, respectively. In the 30 mg/L concentration group, TCF was not detected in the serum of eels 96 hours after bathing, and was below the detection limit after 336 hours in muscle and liver. On the other hand, in the 150 mg/L concentration group, TCF was not detected in the serum of eels 336 hours after bathing, but was detected in muscle and liver at 336 hours. In conclusion, the results of this study would be useful in establishing the MRL of TCF in farmed A. japonica.

Determination of itraconazole in human plasma by high performance liquid chromatography (HPLC/UV를 이용한 혈장 중 이트라코나졸의 분석)

  • Jang, Hae Jong;Lee, Ye Rie;Lee, Kyung Ryul;Han, Sang-Beom;Kang, Seung Woo;Lee, Hee Joo
    • Analytical Science and Technology
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    • v.19 no.3
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    • pp.239-243
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    • 2006
  • This method is used for the determination of itraconazole in human plasma by liquid-liquid extraction and high performance liquid chromatography. Felodipine was used as an internal standard. After extraction of the plasma with diethyl ether, the centrifuged upper layer was then transferred. The supernantant was evaporated and then reconsituted with mobile phase. The mobile phase was composed of 10 mM ammonium acetate adjusted to pH 7 by phosphoric acid with a flow rate of 0.2 mL/min. A C18 reversed-phase column with a pre-column was used as the analytial column. Linear detection responses were obtained for itraconzole concentration range for 2~1,000 ng/mL. The correlation coefficient of linear regression($R^2$) was 0.9991, limit of quantification (LOQ) was 2 ng/mL, reproducibility was less than 10.8 %, and accuracy was 97.2~108.2%. This method has been successfully applied to the pharmacokinetic study of itraconazole in human plasma.

Experiment to Improve Bioavailability and Oral Absorption of Solubilized Curcumin Using Beta-cyclodextrin and Lysine (Beta-cyclodextrin과 Lysine을 이용한 가용화 커큐민 생체 이용률 및 경구 흡수율 개선 확인 실험)

  • Ye Jin Hwang;Hyeon Woo Kim;Seo Kyung Lee;Ji Hoon Park;Sang Yoon Lee;Jae Seon Kang
    • Journal of Life Science
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    • v.34 no.8
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    • pp.548-557
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    • 2024
  • Curcumin, the primary active compound in Curcumae Radix of the ginger family, exhibits a range of therapeutic effects, including blood sugar regulation, immunoregulation, antioxidant, antibacterial, and antitumor activities. However, its poor water solubility and chemical instability result in suboptimal pharmacokinetics with low oral absorption (0.18%) and bioavailability, thus limiting its efficacy. To overcome these limitations, this study aimed to enhance the oral absorption and bioavailability of curcumin by incorporating lysine and β-cyclodextrin. Following oral administration of solubilized cur- cumin, blood samples were collected to assess the oral absorption rate. Solubilized curcumin showed an approximately 1.55-fold increase in absorption at 120 min compared to its non-solubilized form. Furthermore, intravenous administration followed by blood analysis showed a 25-fold increase in bio- availability at 61 min for the solubilized curcumin compared to the non-solubilized variant. In conclusion, employing lysine for dispersion and stabilization, combined with β-cyclodextrin to enhance solubility, significantly improves curcumin's oral absorption and bioavailability. The results of this experiment are expected to lead to the development of herbal medicines and pharmaceuticals that amplify curcumin's anti-inflammatory, anti-tumor, and blood-sugar-regulation effects.

The objective and quantitative analysis of malocclusion : Part 1. Objective malocclusion severity and subjective treatment difficulty (부정교합의 객관적 정량분석: Part 1. 객관적 부정교합 경중도와 주관적인 치료난이도의 상관관계)

  • Joo, Bo-Hoon;Lee, Ki-Soo
    • The korean journal of orthodontics
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    • v.35 no.1 s.108
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    • pp.60-68
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    • 2005
  • The evaluation of malocclusion has to be done quantitatively and qualitatively. This will be lead toward an analysis of malocclusion severity as well as treatment difficulty. The method of proper evaluation of malocclusion severity and treatment difficulty is necessary to assess treatment effect and efficiency for the orthodontists and to establish fundamentals for planning and executing the health-related policies in private and public institutions. The purposes of this study as the first part of the objective and quantitative analysis of malocclusion were 1) to measure treatment difficulty based on the opinions of several orthodontists. and 2) to investigate the relationships between objective malocclusion severity and subjective treatment difficulty 100 pairs of dental casts that had various types and severity of malocclusion were selected from the orthodontic departments of Kyurghee University and Samsung Medical Center The objective malocclusion severity was measured with the PAR (Peer Assessment Rating) index and the subjective treatment difficulty was evaluated by 8 experienced orthodontists. The relationships between objective malocclusion severity and subjective treatment difficulty were statistically evaluated. There were significant relationships between objective malocclusion severity and subjective treatment difficulty especially in the measurements of the upper anterior alignment, the buccal occlusion. the overjet, the overbite and the midline discrepancy en the malocclusion components. The results of this study can provide the background knowledge to develop a new occlusal index. which contains both the malocclusion severity and treatment difficulty for Korean orthodontists.