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유제화에 의한 경구용 항암제인 테가푸르의 장관 임파수송
이용복,남권호,장우익,오인준,고익배,Lee, Yong-Bok,Nam, Kweon-Ho,Chang, Woo-Ik,Oh, In-Joon,Koh, Ik-Bae 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.1
W/O and O/W emulsions of tegafur (50 mg/5 ml/kg) were orally administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary to investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically taken from each subject of mesenteric lymphatic duct cannulated rats. Then, lymph and plasma levels of tegafur and its active metabolite, 5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic lymph transport by the manipulation of a suspected variable was due to a selective delivery to the intestinal lymphatics or an overall increase availability. Therefore, based on a physiologically based pharmacokinetic model which represents the characteristics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reference(13). In comparison with tegafur solution, AUC and mean residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased in O/W emulsion. Lymph flow rates were similar in both solution and W/O emulsion but half in O/W emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion, respectively. And AUC of 5-FU in thoracic lymph for W/O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery or tegafur by W/O emulsion was more effective than that by on emulsion due to its differences or formation ability of chylomicrons.
나프록센의 비선형 체내동태에 미치는 페노바르비탈의 영향
이용복,채명애,고익배 ( Yong Bok Lee,Myung Ae Chae,Ik Bae Koh ) 한국약제학회 1997 Journal of Pharmaceutical Investigation Vol.27 No.2
N/A In order to elucidate the effect of phenobarbital (PB) on the nonlinear pharmacokinetic behavior of naproxen (NAP), we compared the dose dependent hepatic intrinsic clearance, biliary excretion and protein binding of NAP in control rats to those in the PB-pretreated rats which were intraperitoneally pretreated with PB sodium (75 ㎎/㎏) once a day for four days. NAP was injected via femoral (1.5 ㎎/㎏) and portal(0.25, 0.5, 1.5, 15 and 30 ㎎/㎏) vein to the control and PB-pretreated rats, respectively. And also. we measured the plasma free fraction of NAP with the equilibrium dialysis method and the biliary excreted total amounts of NAP in both rats. Plasma free fraction of NAP was decreased in lower concentration than 150 ㎍/㎖ of NAP due to PB pretreatment. In higher concentration, however, plasma free fraction was increased. These in vitro results suggest that the total protein concentration was increased but the total binding capacity of NAP to protein was decreased by PB-pretreatment. The total plasma clearance and the hepatic intrinsic clearance of NAP had similar values in both groups, respectively. And, both clearances of NAP were significantly increased by PB-pretreatment. Even though the plasma free fractions of NAP in both groups were constantly remained within the concentration range according to the increase of administration dose, the hepatic intrinsic clearances of NAP were significantly increased in both groups with the increased dose. And, the biliary excreted total amounts of NAP were significantly increased by PB-pretreatment at the lower dose, but decreased at the higher dose. These in vivo results suggest that NAP represents the uncommon nonlinear pharmacokinetic behavior that the hepatic intrinsic clearance was enhanced with the increased dose, and that PB enhances further the hepatic intrinsic clearance of NAP with the increased dose due to its enzyme induction effect.
흰쥐 분리 간세포에 있어서 딜티아젬의 간클리어런스에 미치는 페노바르비탈의 영향
이용복,오준교,고익배,Lee, Yong-Bok,Oh, Joon-Kyo,Kho, Ik-Bae 한국약제학회 1996 Journal of Pharmaceutical Investigation Vol.26 No.1
In order to study the effect of phenobarbital(PB) on the hepatic transport of diltiazem(DTZ), $Ca^{2+}$ channel blocker, we used isolated hepatocytes of rat which was intraperitoneally pretreated with phenobarbital sodium(75 mg/kg) for four days once a day. For the isolation of rat liver cells, a modification of the two step procedure of Seglen was used. DTZ was dissolved in incubation buffer to the final DTZ concentrations of 200, 400, 600, 800 and 1000 ng/ml in order to elucidate the uptake characteristics of DTZ by hepatocytes. Reactions were stopped at 10, 20, 30, 45, 60, 90, 120 and 300 sec. The initial velocity was determined by disappearance of diltiazem in the hepatocyte suspension. On the other hand, to determine the effect of PB on the in vitro hepatic intrinsic clearance of DTZ we obtained the metabolism rates of DTZ in the control and the PB-pretreated rat hepatocyte at various time intervals. According to pretreatment with PB, the size of hepatocyte and the amount of protein per $10^6$ cells were significantly (p<0.01) increased from $26.92{\pm}0.1364\;m$ to $35.31{\pm}1.00\;m$ and from $468{\pm}6.5\;{\mu}g/10^6$ cells to $628.8{\pm}12.1{\mu}g/10^6$ cells, respectively. In the case or hepatic uptake of diltiazem, $K_m$ was not different in the normalization by cell numbers and increased from $2.90\;{\mu}M\;to\;13.89\;{\mu}M$ in the normalization by protein amount. $V_max$ was increased regardless of normalization by protein amount and cell numbers, from $1.21\;{\mu}mole/min \;{\cdot}\;mg\;protein\;to\;3.96\;{\mu}mole/min\;{\cdot}\;mg\;protein\;and\;from\;2.38\;{\mu}mole/min\;{\cdot}\;10^6\;cells\;to\;2.83\;{\mu}mole/min\;{\cdot}\;10^6\;cells$, respectively. The in vitro hepatic intrinsic clearance of DTZ was significantly (p<0.01) increased from $0.640{\pm}0.038\;ml/mim\;{\cdot}\;10^6\;cells\;to\;2.385{\pm}0.212\;ml/min\;{\cdot}\;10^6\;cells$ due to PB-pretreatment. These results suggest that the uptake of DTZ by hepatocyte is extremely fast and PB enhances the hepatic intrinsic metabolic clearance of DTZ.
SS330 용접재에서 재분포 잔류응력 및 균열닫힘영향을 고려한 파로거동에 관한 연구
이용복,정진성,조남익,Lee, Yong-Bok,Jeong, Jin-Seong,Jo, Nam-Ik 대한기계학회 1996 大韓機械學會論文集A Vol.20 No.7
In this study residual stress in weldment was considered about the effect on the fatigue propagation and about the effect of redistribution of residual stress. Then, fatigue tests were conducted by the center notched specimens machined with welded plate. The residual stress and its redistribution after the crack growth were measured by the magnetizing stress indicator and hole-drilling method. Fatigue crack propagation was estimated by the specimens having residual stress redistributed after the cracks growth and having the effects of crack closure. Crack growth rates were predicted and compared with experimental results. It had been found that the predicted crack propagation rates have a good agreement with experimental results when the redistribution of residual stress was considerd.
탄성 링을 갖는 볼 베어링 지지의 터보 펌프 임계 속도에 관한 연구
이용복,김창호,곽현덕,하태웅,우유철,Lee, Yong-Bok,Kim, Chang-Ho,Kwak, Hyun-Duck,Ha, Tae-Woong,Yoo, Woo-Chul 한국유체기계학회 2001 한국유체기계학회 논문집 Vol.4 No.2
This study was performed to evaluate the dynamic behavior of turbo pump unit. The acceptable separate margin of $1^{st}$ critical speed was obtained by the use of elastic-ring inserted ball bearing, while the poor separate margin of $1^{\st}$ critical speed was appeared in the case without the elastic-ring. In addition, the results show that the stiffness and damping of plain seals give more separate margin of $2^{nd}$ critical speed. However the wear or the failure of seals could reduce the $2^{nd}$ critical speed near the operating speed.
시메티딘이 간혈류량에 미치는 영향 - Rat에 있어서 Indocyanine Green의 체내 동태를 중심으로 -
이용복,고익배,Lee, Yong-Bok,Koh, Ik-Bae 한국임상약학회 1993 한국임상약학회지 Vol.3 No.2
The influence of cimetidine pretreatment(100mg/kg, single i.p.) on the hepatic blood flow was investigated using pharmacokinetic parameters of indocyanine green(ICG) in the rat on the basis of hepacc perfusion-limited model. ICG(1mg/kg) was respectively administered via femoral and portal vein to the control and to the cimetidine-pretreated rats. The rate constant K12, K20 and the systemic clearance(CLt) of ICG were significantly(p<0.05) decreased ill the cimetidine-pretrea-to(B rats, but no significant diffirences were observed in hematocrit and liver weight. The biliary excretion rates of ICG were also decreased regardless of the route of administration in the cimetidine-pretreated rats. And also the hepatic blood flow in rats was decreased about $16\%$ by cimetidine. It may be concluded that the decreased hepatic blood flow with cimetidine mainly contributed to the decreased hepatic uptake and the decreased systemic clearance of ICG.