Aspirin plasma protein binding

Avoid aspirin, as it may increase free T4 and T3 levels by interfering with plasma-protein binding ° Fluid resuscitation... 

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). 

Iopanoic acid is as potent a uricosuric agent as probenecid and this effect might explain some renal complications aspirin reduces the uricosuric effect but can also impair X-ray visualization because of competition at plasma protein-binding sites. Fluctuations of serum urate after oral cholecystography can interfere with diagnostic tests and even precipitate an attack of gout (578). 

Salicylates Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. Salicylates may displace drugs from plasma protein binding sites. Carbonic anhydrase inhibitors [NE] Increased acetazolamide serum concentrations increased salicylate toxicity due to decreased blood pH. 

If warfarin and aspirin are used simultaneously, both drugs appear in the plasma in higher than expected concentrations due to competition for plasma protein binding. This will increase the pharmacological activity of both drugs, but the action of warfarin is of most importance. 

Aspirin i plasma protein binding of methotrexate (a relatively minor contribution to the interaction) and the renal excretion of high doses of methotrexate. Salicylates compete with methotrexate for renal elimination... 

Salicylates are highly bound to plasma protein albumin, with binding being concentration dependent. At low therapeutic concentrations of 100 pg/mL, approximately 90% of aspirin is plasma protein bound, whereas at higher concentrations of approximately 400 pg/mL, only 76% binding is observed. Plasma protein binding is a major factor in the drug interactions observed for salicylates. 

Not fully established. One idea is that these carbonic anhydrase inhibitors (acetazolamide, diclofenamide) affect the plasma pH, so that more of the salicylate exists in the un-ionised (lipid-soluble) form, which can enter the CNS and other tissues more easily, leading to salicylate toxicity. However, carbonic anhydrase inhibitors also make the urine more alkaline, which increases the loss of salicylate (see also Aspirin or other Salicylates + Antacids , p.l35). Animal studies confirm that carbonic anhydrase inhibitors increase the lethal toxicity of aspirin. An alternative suggestion is that because salicylate inhibits the plasma protein binding of acetazolamide and its excretion by the kidney, acetazolamide toxicity, which mimics salicylate toxicity, may occur. ... 

The damaging effects of aspirin and NSAIDs on the gut appear to be additive. The mechanisms behind the pharmacokinetic changes have not been resolved. Changes in the rates of absorption and renal clearance and competition for plasma protein binding have been proposed. 

Aspirin Aspirin is poorly bound to plasma proteins and its apparent volume of distribution is low (10 L). Its metabolite, salicylic acid, is highly bound to plasma proteins, but its binding is concentration-dependent (nonlinear). At low concentrations (less than 100 mcg/mL), approximately 90% of salicylic acid is bound to albumin. Salicylic acid is widely distributed to all tissues and fluids in the body, including the CNS, breast milk, and fetal tissues. 

Multiple drug interactions can occur with the TCA drugs. Because of their high degree of binding to plasma proteins, competition for binding sites can exist between TCAs and phenytoin, aspirin, phenothiazines. 

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. 

Drugs can compete for the same protein binding sites and this is a form of drug interaction. A well-known and important example is that of warfarin and aspirin. Warfarin is an anticoagulant, which binds extensively to plasma proteins, and this is taken into account when dosages are worked out. Aspirin taken with warfarin competes for the same... 

The volume of distribution of usual doses of aspirin averages -170 mUkg of body weight at high therapeutic doses, this volume increases to 500 mUkg because of saturation of binding sites on plasma proteins. Aspirin can be detected in the plasma only for a short time as a result of hydrolysis in plasma, liver, and erythrocytes. 

By expressing drug concentrations as that required to displace 50 per cent of the baseline bound urate, the relative urate displacing capacities can be compared (Table IV). Aspirin is again the most potent urate displacer, probenecid the least. We have subsequently demonstrated a variety of agents which inhibit the binding of urate to plasma proteins and to date all such agents have been uricosuric. Other substances, such as bilirubin, have also been shown to interfere with the urate-plasma protein interaction. 

Albumin is the most abundant protein in human and other animal plasma. It is estimated that up to 40% of the total albumin in humans is in circulation transporting essential nutrients, especially those that are sparingly soluble in aqueous-based plasma. For example, the fatty acids, which are important fuel molecules for the peripheral tissue, are distributed by albumin. In addition, albumin is the plasma transport protein for other substances including bilirubin, thyroxine, and steroid hormones. Also, many drugs including aspirin, sulfanilamides, clofibrate, and digitalis bind to albumin and are most likely carried to their sites of action by the protein. 

Aspirin is rapidly absorbed peak plasma concentrations are achieved within 40 minutes and significant platelet inhibition is observed within an hour. Although the plasma half-life is 20 minutes, irreversible binding and the lack of de-novo protein synthesis in platelets results in COX-1 inhibition for the life span of platelets ( I0 days). The stable metabolite ofTxA2, can be measured in plasma or urine and is a specific indicator of platelet response to aspirin therapy (43,44),... 

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