Hypoalbuminemia protein binding

The free fraction may increase as the total concentration increases, and free concentrations may be more useful than total concentrations, especially at higher concentrations or in patients with hypoalbuminemia. Protein binding is decreased in patients with head trauma. 

AED pharmacokinetic data are summarized in Table 52-3. For populations known to have altered plasma protein binding, free rather than total serum concentrations should be measured if the AED is highly protein bound. Conditions altering AED protein binding include chronic renal failure, liver disease, hypoalbuminemia, burns, pregnancy, malnutrition, displac-... 

The plasma protein binding of diazepam is abont 97 to 99% in adults, regardless of age, but the distribution volnme of around 1 L/kg is higher in the elderly and females. Hypoalbuminemia leads to an increase in the fraction of unbonnd drug in plasma and a faster rate of elimination, as more drug is available for metabolism. 

Roughly 80-90% of the salicylate in plasma is bound to proteins, especially albumin, at concentrations encountered clinically the proportion of the total that is bound declines as plasma concentrations increase. Hypoalbuminemia, as may occur in rheumatoid arthritis, is associated with a proportionately higher level of free salicylate in the plasma. Salicylate competes with a variety of compounds for plasma protein binding sites these include thyroxine, triiodothyronine, penicillin, phenytoin, sulfinpyrazone, bilirubin, uric acid, and other NSAIDs such as naproxen. 

Protein binding 90% protein bound to albumin, = 0.1 Unbound phenytoin plasma concentrations correlate with effect and toxicity. A decrease in protein binding occurs due to hypoalbuminemia or protein binding displacement interactions. 

Hypoalbuminemia and altered plasma protein binding increase free or unbound concentrations of drugs... 

Drug distribution in elderly patients may be altered by hypoalbuminemia, qualitative changes in drug-binding sites, reductions in relative muscle mass, increases in the proportion of body fat, and decreases in total body water. The plasma level of free, active drug is often a direct function of the extent of drug binding to plasma proteins. There is a well-documented age-dependent decline (about 20%) in plasma albumin concentration in humans due to a reduced rate of hepatic albumin... 

The binding sites of the protein are not unlimited and are subject to saturation. When this occurs, toxicity may develop following further drug administration, because the later portion of the drug remains free. Consistent with this view is the observation that toxic manifestations of drugs are quite frequent and considerably higher in individuals suffering from hypoalbuminemia, or altered plasma and tissue protein concentrations, or both. 

Triamterene is about 45 to 70% bound to plasma proteins.2 91 Influence of disease on binding of triamterene to plasma proteins has been studied.92 Plasma from uremic patients had a decreased binding of triamterene. Hypoproteinemia and hypoalbuminemia decreased the binding fraction. Drug binding was impaired by cirrhosis also.92... 

Phenytoin is extensively (-90%) bound to serum proteins, mainly albumin. Small variations in the bound fraction dramatically affect the absolute amount of free (active) drug increased proportions of free drug are evident in the neonate, in patients with hypoalbuminemia, and in uremic patients. Some agents e.g., valproic acid) can compete with phenytoin for binding sites on plasma proteins when combined with valproate-mediated inhibition of phenytoin metabolism, marked increases in free phenytoin can result. 

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