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원보 ; 총수담관 결찰에 의한 간외 담즙분비정체가 흰쥐의 간기능에 미치는 영향에 대한 약물속도론적 분석
Original Articles ; Pharmacokinetic Analysis of the Effect of Extrahepatic Cholestasis by Common Bile Duct Ligation on Hepatic Function in Rats
이용복 , 나은영 , 주은희 , 정숙진 , 고익배 ( Yong Bok Lee , Eun Yeong Na , Eun Hee Joo , Sug Jin Jeong , Ik Bae Koh )
약제학회지 25권 3호 193-204(12pages)
UCI I410-ECN-0102-2008-510-000814609

In order to examine the effect of extrahepatic cholestasis induced by common bile duct ligation on the hepatic function, the pharmacokinetics of antipyrine and d-propranolol were investigated in rats. In addition, in an attempt to observe the degree of direct hepatic injury, light and electron microscopic observations and conventional pathologic test using serum were performed. Five days after common bile duct ligation, antipyrine(15 ㎎/㎏) and d-propranolol(3 ㎎/㎏) were intravenously administrated to the rats, respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased. Because hepatic clearance of antipyrine poorly extracted by the liver and that of d-propranolol highly extracted by the liver are respectively dependent on the hepatic intrinsic clearance and the hepatic blood flow, it may be concluded that extrahepatic cholestasis following five days after common bile duct ligation decreased the hepatic intrinsic clearance and the hepatic blood flow. SGPT, SGOT, cholesterol, bilirubin(total bilirubin. direct bilirubin) and alkaline phosphatase were significantly increased(p<0.05). The proliferation of bile ducts was prominent, and degeneration and necrosis of hepatocytes were observed by light microscope. Also, ultrastructurally, bile canaliculi were containing the amorphous materials and losing microvilli. and SER and RER in hepatocytes were dilated and vacuolated.

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