Protein-binding displacement

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Rolan PE. Plasma protein binding displacement interactions - why are they still regarded as clinically important Br ] Clin Pharmacol 1994 37 125-8. 

Christensen, H., Baker, M., Tucker, G.T. and Rostami-Hodjegan, A. (2006) Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug-drug interactions from in vitro data. Journal of Pharmaceutical Sciences, 95, 2778-2787. 

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

Rolan, P. E. Plasma Protein Binding Displacement Interactions Why Are They Still Regarded as Clinically Important Br. J. Clin. Pharm. 1994, 37, 125-128. 

Rosenthal AE (1967) A graphic method for the determination and presentation of binding parameters in a complex system. Analytical Biochemistry 20 525-532 Sansom LN, Evans AM (1995) What is the True Clinical Significance of Plasma Protein Binding Displacement Interactions Drug Safety 12(4) 227—233 Scatchard G (1949) The attractions of protein for small molecules and ions. New York Academic of Sciences 51 660-692... 

Distribution Water/fat Protein binding % Displaced by bilirubin or displaces bilirubin... 

Sansom LN, Evans AM. What is the true clinical significance of plasma protein binding displacement interactions Drug Saf 1995 12 227-33. 

Bepridil has been the subject of a brief general review (1) and its pharmacokinetics have been specifically reviewed (2). Although it is highly protein-bound, bepridil does not take part in protein-binding displacement interactions (2). 

The authors did not propose a mechanism for this interaction, although the rapidity of the effect suggests protein binding displacement of warfarin nor did they comment on the possible role of the extract of broccoli, which contains vitamin K. 

Extensive (but weak) plasma protein binding - displacement by other drugs may increase free fraction —anticoagulant effects. 

Possible Increase That Plasma Protein Binding Displacement Could Make in a Victim Drug s Pharmacodynamic Effect as a Function of the Extent of Plasma Protein Binding of the Victim Drug... 

This means that overall exposure to unbound drug can t be affected by plasma binding or plasma protein binding displacement interactions. Furthermore, if the drug is a high hepatic extraction-ratio drug, such that CLint >Qj then Q hepatic blood flow rate, becomes limiting, and Equation (12.31) becomes ... 

An interaction involving protein binding displacement may occur with aspirin. 

At a fundamental level, a determination must be made whether a biological mechanism for an interaction exists. The most common pharmacokinetic mechanisms include metabolic inhibition or induction, protein binding displacement, and interference with absorption. Potential pharmacodynamic synergy or antagonism must also be considered. Interactions must be considered from the perspective of... 

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. 

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