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KMID : 0043319900130030233
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Archives of Pharmacal Research
1990 Volume.13 No. 3 p.233 ~ p.239
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Effect of Uranyl Nitrate-Induced Acute Renal Failure on the Pharmacokinetics of Sulfobromophthalein in Rats
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Park GH
Shim CK
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Abstract
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The effect of acute renal failure (ARF) on the pharmacokinetics of sulfobromophthalein (BSP) was investigated in order to elucidate if renal failure modifies the hepatic metabolism of drugs. ARF was induced by intravenous (iv) injection of uranyl nitrate (UN) to rats (5mg/kg) five days before the experiment. Area under the plasma concentration-time curve (AUC) of BSP after portal vein (pv) injection increased by 2-fold and total body clearance (CLt) decreased one half (p < 0.01) in UN-induced ARF (UN-ARF) rats compared to the control rats. But the plasma disappearance of BSP after iv injection did not differ significantly between control and UN-ARF rats. Since BSP is excreted via the liver, CLt representd the approximate hepatic clearance of BSP. Therefore, the decrease in CLt represents a decrease in hepatic intrinsic clearance (CLint) for BSP since plasma free fraction (fp) of BSP was not affected by UN-ARF. The content of hepatic cytoplasmic Y-protein, which catalyzes BSP-glutathione conjugation and limits the transfer of BSP from blood to bile, increased significantly (p < 0.01), however its binding activity (BA) for BSP was decreased significantly (p < 0.01) by UN-ARF. The decrease in CLint, might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP.
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KEYWORD
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