Phenytoin displacement

Phenytoin displaces bupivacaine from plasma proteins (28). 

At r = 6 min, 5 p,L of serum were injected. As it flowed through the column, free phenytoin displaced some fluores-cently labeled phenytoin from the silica. Fluorescence was measured at 820 nm with laser excitation at 785 nm. 

Phenobarbital, phenytoin, primidone, and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate glucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzyme systems and displaces some drugs from plasma albumin. 

An immunosensor based on a competitive fluorescence energy-transfer immunoassay was reported by Anderson 105) for the measurement of phenytoin. Texas red-labeled antibody was incubated with a phenytoin derivative. On displacement of the derivative by the antigen, the change in the fluorescence signal was recorded. Detection limits approached 5 /iM with response times ranging from 5 to 30 min. 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

An understanding of absorption, binding, metabolism, and excretion is more important for phenytoin than it is for most drugs. Following oral administration, phenytoin absorption is slow but usually complete, and it occurs primarily in the duodenum. Phenytoin is highly bound (about 90%) to plasma proteins, primarily plasma albumin. Since several other substances can also bind to albumin, phenytoin administration can displace (and be displaced by) such agents as thyroxine, triiodothyronine, valproic acid, sulfafurazole, and salicylic acid. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

Phenytoin [NE] Enzyme induction anticoagulant effect may increase transiently at start of phenytoin therapy due to protein-binding displacement. 

Drugs may compete for binding sites on the plasma or tissue protein, or may displace previously bound drugs. For example, phenylbutazone may compete with phenytoin for binding to albumin. 

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

Valproate Phenytoin Total serum phenytoin concentration underestimates the unbound phenytoin concentration toxicity can occur in some patients Displacement of phenytoin from plasma proteins, sometimes associated with inhibition of phenytoin metabolism... 

Azapropazone Phenytoin Risk of phenytoin toxicity altered relation between total phenytoin concentration and effect Displacement from plasma proteins and inhibition of phenytoin metabolism... 

Ibuprofen Phenytoin Interaction probably of little or no clinical significance Displacement from plasma protein binding sites... 

Phenylbutazone Phenytoin Valproate Risk of toxicity, particularly with phenytoin altered relation between total concentration and effect Displacement from plasma protein binding sites and inhibition of metabolism of the affected drugs... 

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