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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.
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나프록센의 비선형 체내동태에 미치는 페노바르비탈의 영향
이용복,채명애,고익배 전남대학교 약품개발연구소 1997 약품개발연구지 Vol.6 No.1
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.
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