Valproic Acid Binding to Human Serum Albumin and Determination of Free Fraction in the Presence of Anticonvulsants and Free Fatty Acids

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Abstract
The interaction between valproic acid (VPA) and human serum albumin (HSA) was investigated using the equilibrium dialysis technique under various conditions. Solutions of VPA in HSA (2 .times. 10-4 M) were dialyzed against isotonic phosphate buffer at 37.degree. C. Protein and buffer compartments were assayed for VPA by GLC. The free fraction (.alpha.) of VPA increased from 0.13 at 27 .mu.g/ml to 0.49 at 103 .mu.g/ml. Scatchard plots were linear, indicating the existence of one type of binding site. The mean (.+-. percent SD) number of binding sites per macromolecule was 2.06 .+-. 3.7% and the mean (.+-. percent SD) association constant was 2.69 .times. 104 .+-. 15.0% l/mol. The effects of 3 anticonvulsants (phenytoin, phenobarbital, and carbamazepine) and 4 major free fatty acids (FFA) (stearic, palmitic, oleic, and linoleic) on .alpha. were studied. The free fraction, 0.18, was not affected by phenobarbital (20 and 40 .mu.g/ml), carbamazepine (10 and 20 .mu.g/ml) or phenytoin (20 and 40 .mu.g/ml). Each of the 4 FFA caused a significant increase in .alpha.: 19-48% increase at 100 .mu.g/ml of FFA and 88-118% at 200 .mu.g/ml.

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