Valproic acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsants and free fatty acids. 1979

I H Patel, and R H Levy

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 x 10(-4) M) were dialyzed against isotonic phosphate buffer at 37 degrees C. Protein and buffer compartments were assayed for VPA by GLC. The free fraction (alpha) of VPA increased from 0.13 at 27 microgram/ml to 0.49 at 103 microgram/ml. Scatchard plots were linear, indicating the existence of one type of binding site. The mean (+/- % SD) number of binding sites per macromolecule was 2.06 +/- 3.7% and the mean (+/- % SD) association constant was 2.69 x 10(4) +/- 15.0% liters/mole. The effects of three anticonvulsants (phenytoin, phenobarbital, and carbamazepine) and four 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 microgram/ml), carbamazepine (10 and 20 microgram/ml) or phenytoin (20 and 40 microgram/ml). Each of the four FFA caused a significant increase in alpha: 19--48% increase at 100 microgram/ml of FFA and 88--118% at 200 microgram/ml.

UI MeSH Term Description Entries
D008041 Linoleic Acids Eighteen-carbon essential fatty acids that contain two double bonds. Acids, Linoleic
D009829 Oleic Acids A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon. Octadecenoic Acids,Acids, Octadecenoic,Acids, Oleic
D010169 Palmitic Acids A group of 16-carbon fatty acids that contain no double bonds. Acids, Palmitic
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
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
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
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
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

Related Publications

I H Patel, and R H Levy
September 1987, Revista espanola de fisiologia,
I H Patel, and R H Levy
January 1980, Acta pharmaceutica Suecica,
I H Patel, and R H Levy
May 1991, International journal of clinical pharmacology, therapy, and toxicology,
I H Patel, and R H Levy
June 1984, British journal of clinical pharmacology,
I H Patel, and R H Levy
February 1998, Biological & pharmaceutical bulletin,
Copied contents to your clipboard!