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  • Title: Displacement effect of valproate on bilirubin-albumin binding in human plasma.
    Author: Yu HY, Shen YZ.
    Journal: J Formos Med Assoc; 1999 Mar; 98(3):201-4. PubMed ID: 10365540.
    Abstract:
    Drugs that can displace bilirubin from plasma albumin binding may cause various late manifestations of brain damage if given to newborns with unconjugated hyperbilirubinemia. The purpose of this study was to examine the displacement effect of valproate (VPA) on bilirubin-albumin binding in human serum albumin (HSA) and human plasma. Bilirubin-HSA solution and bilirubin-plasma solution containing no or serial concentrations of VPA were prepared, and free bilirubin in these solutions was measured by the enzyme oxidation method. VPA displaced bilirubin from bound bilirubin-albumin. The binding constant (KD) of VPA to the high affinity bilirubin-binding site of HSA and plasma protein were 11.6 L/mmol and 9.0 L/mmol respectively. The displacement effect may occur at the clinical concentration range of VPA, with a maximal displacing factor of 1.5 to 4.7. These results suggest that the clinician should use VPA in jaundiced neonates with caution.
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