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Serum protein binding of valproic acid in healthy subjects and in patients with liver disease. 1981

S Urien, and E Albengres, and J P Tillement

The binding parameters of valproic acid (VPA) to human serum albumin (HSA) were determined by equilibrium dialysis and computed using non-linear regression. However unclassic, it was observed that the binding parameters of VPA varied according to the concentration of the HSA solutions used. At 580 microM HSA, VPA is bound to two classes of binding sites with the association constants K1 = 56000 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 microM palmitate, 250 microM clofibrate, 320 microM phenylbutazone, or 360 microM salicylate. In any case, the increase of the VPA serum free fraction is highly correlated with the inhibitor concentration. On the other hand, the free serum fraction of warfarin is increased by 600 microM VPA (100 micrograms/ml). In patients with liver disease, the variations of the free serum fraction of VPA are correlated to the albumin and to the bilirubin concentrations. Serum binding of VPA is significantly decreased in the two groups of patients as compared with the control group.

UI MeSH Term Description Entries
D008107 Liver Diseases Pathological processes of the LIVER. Liver Dysfunction,Disease, Liver,Diseases, Liver,Dysfunction, Liver,Dysfunctions, Liver,Liver Disease,Liver Dysfunctions
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005230 Fatty Acids, Nonesterified FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form. Fatty Acids, Free,Free Fatty Acid,Free Fatty Acids,NEFA,Acid, Free Fatty,Acids, Free Fatty,Acids, Nonesterified Fatty,Fatty Acid, Free,Nonesterified Fatty Acids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D012709 Serum Albumin A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules. Plasma Albumin,Albumin, Serum
D014635 Valproic Acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS. Dipropyl Acetate,Divalproex,Sodium Valproate,2-Propylpentanoic Acid,Calcium Valproate,Convulsofin,Depakene,Depakine,Depakote,Divalproex Sodium,Ergenyl,Magnesium Valproate,Propylisopropylacetic Acid,Semisodium Valproate,Valproate,Valproate Calcium,Valproate Sodium,Valproic Acid, Sodium Salt (2:1),Vupral,2 Propylpentanoic Acid

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