Effect of uranyl nitrate-induced acute renal failure on the pharmacokinetics of sulfobromophthalein in rats |
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Authors: | Gun-Hwa Park Chang-Koo Shim |
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Institution: | (1) College of Pharmacy, Seoul National University, 151-742 Seoul, Korea |
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Abstract: | 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 (5 mg/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 (CL
t) decreased one half (p<0.01) in UN-induced ARF (UN-ARF) rats compared to the control rats. But the plasma disappearance of
BSP afteriv injection did not differ significantly between control and UN-ARF rats. Since BSP is excretedvia the liver,CL
t representd the approximate hepatic clearance of BSP. Therefore, the decrease inCL
t represents a decrease in hepatic intrinsic clearance (CL
int) for BSP since plasma free fraction (f
p) 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 inCL
int might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP. |
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Keywords: | Acute renal failure (ARF) uranyl nitrate sulfobromophthalein (BSP) pharmacokinetics protein binding Y-protein |
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