SERUM-PROTEIN BINDING OF VALPROIC ACID IN HEALTHY-SUBJECTS AND IN PATIENTS WITH LIVER-DISEASE

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 19  (7) , 319-325
Abstract
The binding parameters of valproic acid (VPA), an antiepileptic drug, to human serum albumin (HSA) were determined by equilibrium dialysis and computed using a non-linear regression. The binding parameters of VPA varied according to the concentration of the HSA solutions used. At 580 .mu.M HSA, VPA is bound to 2 classes of binding sites with the association constants K1 = 56,000 M-1 and K2 = 750 M-1, and their respective numbers of binding sites n1 = 2 and n2 = 5. Free serum fraction of VPA is significantly increased by 500, 1000, and 1500 .mu.M palmitate, 250 .mu.M clofibrate, 320 .mu.M phenylbutazone, or 360 .mu.M salicylate. The increase of the VPA serum free fraction is highly correlated with the inhibitor concentration. The free serum fraction of warfarin is increased by 600 .mu.M VPA (100 .mu.g/ml). In patients with liver disease, the variations of the free serum fraction of VPA are correlated to the albumin and bilirubin concentrations. Serum binding of VPA is significantly decreased in the 2 groups of patients compared with the control group.