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KMID : 0369819950250030193
Jorunal of Korean Pharmaceutical Sciences
1995 Volume.25 No. 3 p.193 ~ p.204
Pharmacokinetic Analysis of the Effect of Extrahepatic Cholestasis by Common Bile Duck Ligation on Hepatic Function in Rats





Abstract
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(15mg/kg) and d-proprnaolol(3mg/kg) were intravenously
administrated to
rats. respectively. The total clearances of antipyrine and d-propranolol were significantly(p<0.05) decreased, Because hepatic clearanceof antipyrine poorly extracted bythe 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 cholestatsis following five days after common bile duct ligation decreasedthe 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 proliferationof bile ducts was prominent, 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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