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Pharmacokinetic Interaction between Warfarin and Efonidipine in Rats

  • Choi, Dong-Hyun;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.41 no.5
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    • pp.273-278
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    • 2011
  • The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.

A Case of Intestinal Lymphangiectasia (장림프관 확장증 1례)

  • Yim, Hyung Eun;Jung, Min Ji;Yoo, Kee Hwan;Hong, Young Sook;Lee, Joo Won;Kim, Soon Kyum
    • Clinical and Experimental Pediatrics
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    • v.46 no.9
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    • pp.921-925
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    • 2003
  • Intestinal lymphangiectasia, one of the protein-losing gastroenteropathies, is an uncommon disease characterized by dilated intestinal lymphatics, enteric protein loss, edema, hypoalbuminemia, and lympocytopenia. Small bowel biopsy and CT have been used to confirm the diagnosis of intestinal lymphangiectasia. Small bowel biopsy shows collections of abnormal dilated lacteals in submucosa with distortion of villi and CT findings have been described as diffuse nodular thickening of the small bowel and as linear hypodense streaking densities in the small bowel caused by dilated lymphatic channels. Demonstration of increased enteric protein loss using $^{51}Cr-$, $^{131}I-$ or $^{99m}Tc-labeled$ albumin, timed measurement of fecal excretion of radioactivity or by measuring fecal clearance of alpha 1-antitrypsin can also help the diagnosis. We experienced a rare case of intestinal lymphangiectasia in an eight year old boy who presented with facial edema, abdominal distension and intermittent diarrhea. We report a patient with intestinal lymphangiectasia, in whom abdominal CT, $^{99m}Tc-labeled$ albumin scintitigraphy, and stool alpha 1-antitrypsin measurement played key roles in determining the diagnosis. A brief review of literature was made.

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

  • Park, Min-Ho;Shin, Seok-Ho;Byeon, Jin-Ju;Lee, Gwan-Ho;Yu, Byung-Yong;Shin, Young G.
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.107-115
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    • 2017
  • Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

An Evaluation Method for Short-Term Ratings of Double-Circuit Overhead Transmission Lines (2회선 가공송전선의 단시간정격에 관한 평가방법)

  • Kim, Sung-Duck;Sohn, Hong-Kwan;Jang, Tae-In
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.21 no.7
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    • pp.20-28
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    • 2007
  • This paper describes an analytical method to determine the short-term ratings to reliably operate the overhead transmission lines with double-circuit lines when faulting one circuit of the two. As linearizing the thermal equilibrium equation that represents the temperature characteristic of conductors, we show that the linear equation can be easily represented the over-current and it's temperature property during overloading the one line. Generally, it is well hewn that the short-term line ratings should be determined by considering both conductor life and dip. However, most power companies have their own different guides for the short-term ratings. Using the suggested method in this paper, it can be re-accessed the short-term ratings given in Kepco's overhead transmission lines constructed during the past three different periods. As a result, it is verified that the short-term ratings could be increased mil efficiently. Furthermore, it would be directly applied the given method to determine the short-term dynamic line ratings when occurring faults in one of the double-circuit lines, without doing my other actions for the current lines.

Effect of dietary Calcium Level on Cadmium and Lead Toxicity in Rats (식이내 Calcium 수준이 흰쥐의 카드뮴과 납중독에 미치는 영향)

  • 김미경
    • Journal of Nutrition and Health
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    • v.29 no.9
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    • pp.958-970
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    • 1996
  • This study was performed to investigate the effect of dietary calcium level on cadmium and lead toxicity in rats. Fifty-four male rats of Sprague-Dawely strain weighing 152$\pm$12g were blocked into 9 groups according to body weight, and were raised for 30 days. Nine experimental diets different with cadmium(0%, 0.04%), lead (0%, 0.071%) and calcijm(0.5%, 1.0%, 1.5%) levels were prepared. The results are summarized as follow. Weight gain, F.E.R.(food efficiency ratio), and weights of liver, kidney and femur were lower in cadmium exposed groups than those of heavy metal free groups. Weight gain F.E.R. and ash weight of lead groups were lower than those of heavy metal free groups. But, these were increased with increasing dietary calcium level. Cadmium and lead concentrations in blood, liver, kidney and femur were lower in rats fed 1.5% calcium than 0.5% calcium diet. Fecal cadmium and lead excretions were remarkably increased in 1.5% calcium groups, and cadmium and lead retention rates were decreased in 1.5% calcium groups. Metallothionein concentrations in liver, kidney and small intestine were higher in rats exposed to cadmium and lead. Calcium content in blood, femur and daily urinary and fecal calcium excretion were decreased by cadmium and lead additions, and increased in 1.5% calcium groups. Creatinine clearance were decreased with cadmium administratino and calcium addition. In conclusion, weight gain and organ weights were decreased with cadmium or lead administration. But, cadmium administration was more toxic than lead adminstration. Cadmium or lead toxicity was alleviated by increasing dietary calcium level. Especially, lead toxicity was alleviated in proportion to dietary calcium level.

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Effect of Adenosine Analogues on the Renal Function and Renin Release (가토의 신장기능과 Renin분비에 미치는 Adenosine Analogues의 영향)

  • Song, Yun-Sik;Choi, Byung-Soo;Kim, Suhn-Hee;Cho, Kyung-Woo
    • The Korean Journal of Physiology
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    • v.22 no.2
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    • pp.319-332
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    • 1988
  • The regulations of renal function and renin release are influenced by neural, humoral and physical factors. During the last decade, considerable progress has been made in the identification and characterization of these extrinsic renal control systems. Mechanisms intrinsic to the kidney are also important for renal function. These include the autoregulation of blood flow, and the local control of renin secretion. Fundamental questions regarding the mechanism of these intrinsic controls remain unanswered. Recently, endogenous renal adenosine has been claimed to influence the tubuloglomerular feedback control and renin release. Two subclasses of adenosine receptors $A_1{\;}and{\;}A_2$ have been described. The present experiment was carried out to evaluate the effects of $N_6-cyclohexyladenosine$ $(CHA,{\;}A_1{\;}selective)$ and 5'-N-ethylcarbox-amide adenosine $(NECA,{\;}A_2{\;}selective)$ on the renal function and renin release in the unanesthetized rabbit. Intra-renal arterial infusion of NECA $(0.3{\sim}10.0n{\;}mole/min/rabbit)$ or CHA $(0.03{\sim}10.0n{\;}mole/min/rabbit)$ caused a prompt and dose-dependent decrease in urine volume, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), electrolyte excretion and free water clearance $(CH_2O)$, the effect being much more profound with CHA than with NECA. The NECA infusion resulted in a profound decrease of systemic blood pressure, but the CHA infusion did not. Both NECA and GHA infusions caused a prompt and dose-dependent decrease in renin secretion rate, again the effect being greater with CHA than with NEGA. These results suggest that both $A_1{\;}and{\;}A_2$ adenosine receptors may be involved in the intrinsic control of renal function and renin release, and that the $A_1$ receptors plays a more important role than the $A_2$ receptor in the regulation of renal fnction.

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Alternatives for Entering into the Chinese Market by Smaller-Sized Korean Logistics Enterprises (우리나라 중소물류기업의 중국진출 활성화 방안)

  • Cho, Sam-Hyun
    • Journal of Navigation and Port Research
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    • v.36 no.10
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    • pp.889-893
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    • 2012
  • The growth of Chinese logistics market has brought many logistics enterprises enter into the chinese market. The purpose of this study is to suggest some alternatives for activating enter into chinese market for smaller-sized korean logistics enterprise. First of all, in order to achieve such a purpose, factors for activation through literature survey and previous studies are analyzed. After that, questionnaire survey are carried out. Also factor analysis and reliability test based on the questionnaire results are performed. Main findings are suggested as followings. First, in order to activate entering the chinese market, it is drawn out that possessing of logistics infrastructure and understanding of culture of chinese relationship are most important. Second, market information and reform of management system, inspection and customs clearance are suggested as less important.

Diuretic Action of Vasopressin (바소프레신의 이뇨작용)

  • Go, Seok-Tae;Yun, Jae-Gyeong;Yu, Gang-Jun
    • YAKHAK HOEJI
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    • v.40 no.4
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    • pp.468-477
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    • 1996
  • Vasopressin which is an antidiuretic hormone in human body produced the diuretic action in dog. This study was investigated in order to certify the diuretic action and to search out the mechanism of the action on the vasopressin. Vasopressin, when given in a dose of 10.0mU/kg, bolus+1.0mU/kg/min intravenously, exhibited the increase of urine flow(Vol), renal plasma flow(RPF), osmolar clearance (Cosm) and amounts of sodium and potassium excreted in urine ($E_{Na},\;E_K$), the decrease of reabsorption rate of sodium and potassium in renal tubules ($R_{Na},\;R_K$), and then elevated the mean arterial pressure(MAP). Vasopressin given in a increased dose to 30.0mU/kg, bolus+1.0mU/kg/min intravenously elicited the same aspect with that exhibited by a small dose in changes of Vol. and all renal function and potentiated the change rates, whereas this time MAP did not change at all when compared with control value. Vasopressin, when administered into a renal artery, did not induce the changes of Vol and all renal function in experimental (administered) kidney, but increased slightly the Vol, glomerular filtration rate(GFR), $E_{Na},\;and\;E_K$ expected the no change of $R_{Na}\;and\;R_K$ in the control (not administered) kidney. Vasopressin, when infused into carotid artery, showed the increase of Vol. GFR, $E_{Na},\;and\;E_K$ and no change of $R_{Na}\;and\;R_K$ in a dose of 1/5 of intravenous dose. Diuretic action of vasopressin administered into carotid artery was not influenced by renal denervation. Above results suggest that vasopressin produced diuretic action by hemodynamic changes in dogs. These hemodynamic changes may be mediated by central endogenous substances not associated with renal nerve.

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A NAT for reliable HCV RNA detection from plasma and plasma-derived medicinal products

  • Yoo, Si-Hyung;Jung, Sa-Rah;Park, Su-Jin;Kim, Sun-Nam;Hong, Choong-Man;Lee, Ki-Hong;Oh, Ho-Jung;Kang, Hye-Na;Shin, In-Soo;Choi, Seoung-Eun;Hong, Sung-Ran;Lee, Seok-Ho;Hong, Seung-Hwa
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.300.2-301
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    • 2002
  • HCV is transmitted via various plasma-derived medicinal products. The transmission of HCV could. however, be prevented by screening plasma pools with NAT and validating HCV viral clearance during the manufacturing of plasma derivatives, Although various screening methods including commercial kits are available. it is yet to develop an analytical method to detect HCV in both plasma and plasma derivatives. The objective of this study was to develop a reliable in house method for reliable for the HCV RNA detection from plasma and plasma derivatives. (omitted)

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A Study on Assuring the Effectiveness of Administrational Regulation and Supervision in Korea Private Security (민간경비에 대한 행정규제 및 감독의 실효성 확보 방안)

  • Lee, Sang-Chul;Shin, Sang-Min;Lee, Min-Hyong
    • Korean Security Journal
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    • no.12
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    • pp.245-269
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    • 2006
  • The suggestions that follow are about the device to assure the effectiveness of administrational regulation and supervision in Korean private security. First, government clearance should be reinforced. For this it is necessary that the qualification for security dealer-careers and academic backgrounds with security etc.- should be elucidated in Security Law. Also it should be achieved to increase the capital fund and to keep security guards for insuring substitutional manpower. Second, after legal permission governmental supervision should be done in quality by means of setting up the competent institutions independently. Third, the punishment for obtaining security license mendaciously, carrying out illegal or unfair task and assigning Security Guard Supervisors expediently should be strengthened. Also to prevent expedient acts it is necessary to prescribe illegal or unfair acts in the concrete in Security Law and violators should be legally responsible. Fourth, to lay the foundation for security industry itself and make up for perfunctory governmental direct System for Professional License (of private security guard) should come into effect.

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