| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
In patients with complete bile duct obstruction, the only pathway of bile acid elimination is by the urine. However urinary excretion of cholephilic compounds with bile duct obstruction has not been clarified. Therefore, the urinary excretion of bile acids and organic anions and cations was compared in bile duct-ligated rats for 3 days. After urinary bladder cannulation, radiolabeled materials were intravenously injected, and urine samples were collected every 1-2 hrs for 4-6 h and radioactivity was counted. Urinary excretion (cumulative %dose during 6 h) of taurocholate and cholate was similar (19.3% and 16.8%). Urinary excretion of tauroursodeoxycholate, lithocholate and taurolithocholate-sulfate was less effective (12.7 %, 9.8 % and 2.1%, respectively). Urinary excretion (cumulative %dose during 4 h) of pravastatin was markedly increased in bile duct-ligated rats (86%) compared with control rats (5.5%). Similar but less prominent differences were observed with temocapril (51% and 22
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% in bile duct-ligated and control rats, respectively). Urinary excretion (cumulative %dose during 4 h) of erythromycin was markedly increased in bile duct-ligated rats (49%) compared with control rats (1.9%). Less prominent differences were observed with vinbiastine (18% and 7.4% in bile duct-ligated and control rats, respectively). These results indicate that unconjugated bile acids were taken up by the liver and excreted into blood after further biotransformation even under complete bile duct obstruction. Although bile acid sulfates are major bile acids in the urine of patients with obstructive jaundice, monohydroxylated bile acids are considered to be not so effectively excreted into the urine even with conjugation with taurine and sulfate in rats. The elimination of organic anions and cations are also compensated for by the urinary excretion in bile duct-ligated rats, the extent of the compensation was different among compounds, possibly due to the changes of renal transporter for these compounds in cholestasis. Less
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