Biomaterial Database

Temperature dependence of phenytoin-protein binding in serum: effects of uremia and hypoalbuminemia. 1988

T B Allison, and T J Comstock

Laboratory Service, McGuire VA Medical Center, Richmond 23249.

Phenytoin-protein binding was determined as a function of temperature in uremic patients with normal albumin and in uremic patients with hypoalbuminemia. Free phenytoin levels were determined in ultrafiltrates (MPS-1; Amicon, Lexington, MA, U.S.A.) from serum equilibrated at either 20, 25, 30, 35, or 40 degrees C. Scatchard analyses showed significant differences in phenytoin-protein binding affinity as a function of temperature. Linear regression plots of free phenytoin versus temperature showed the slopes of the uremic and uremic with hypoalbuminemia patients (0.546 and 0.535, respectively) to be 3 times that of patients with normal renal function (0.174). Free phenytoin was analyzed in 150 patients with normal renal function in whom the total phenytoin was in the range of 38.0-80.8 mumol/L. The ultrafiltrate, prepared at 22 +/- 0.5 degrees C, resulted in free phenytoin levels in the range of 3.2-8.3 mumol/L. We have established this as the therapeutic range for the patient population seen at this medical center.

UI	MeSH Term	Description	Entries
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
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D014511	Uremia	A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.	Uremias