INCREASED AVAILABILITY OF PROPRANOLOL IN RATS WITH URANYL NITRATE-INDUCED ACUTE RENAL FAILURE

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The effect of acute renal failure (ARF) on the pharmacokinetics of propranolol was investigated. The model of ARF was produced by the subcutaneous injection of uranyl nitrate to rats (10 mg/kg) and was used 3 d after treatment. Uranyl nitrate-treated rats showed significantly higher plasma concentrations of propranolol after oral administration and the area under the plasma concentration-time curve increased about 3-fold compared to control rats. The plasma disappearance of propranolol after intravenous administration did not differ significanly between control and ARF. The mean availability of propranolol after oral administration increased from 0.120 in control to 0.215 in ARF (p<0.005). Absorption of propranolol was almost complete and no significant difference was found between two groups. No changes in plasma protein binding of propranolol and hepatic blood flow were observed in ARF. On the other hand, hepatic clearance of propranolol determined by liver perfusion studies showed a significant reduction in ARF and the calculated intrinsic clearance of unbound propranolol at a dose of 6.25 mg was 26.8±2.3 ml/min in control and 16.0±2.3 ml/min in ARF (p<0.01). These results demonstrate that the oral availability of propranolol increased in ARF due to a reduction in the hepatic presystemic elimination as compared to healthy control rats.
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