Protein-displacement drug interactions

Finally, free drug levels may be affected by interaction with other medications, which may cause displacement of a drug off the protein. Considering that the elderly are taking more medications, they are more likely to experience protein-displacement drug interactions. However, protein-displacement interactions are not considered as clinically significant as metabolism interactions. 

Devane, C.L., Clinical significance of drug plasma protein binding and binding displacement drug interactions, Psychopharmacol. Bull., 36, 5, 2002. 

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

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. 

Distribution - The binding of oseltamivir carboxylate to human plasma protein is low (3%). The binding of oseltamivir to human plasma protein is 42%, which is insufficient to cause significant displacement-based drug interactions. /Wefabo//sm- Oseltamivir is extensively converted to oseltamivir carboxylate by... 

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. 

MacKichan, J.J. (1989) Protein binding drug displacement interactions—fact or fiction Clin Pharmacokinet 16 65-73. 

The most important drug interaction caused by displacement from plasma proteins occur with coumarin anticoagulants. Phenylbutazone displaces warfarin from its... 

MacKichan JJ. Protein binding drug displacement interactions fact or fiction Clin Pharmacokinei 1989 16 65-73. 

If a second medication is added—whether for psychiatric purposes or for a concurrent medical problem— there is always the possibility of drug interactions. If the new medication is highly protein-bound, it can compete for the proteins occupied by the first medication and in fact displace some of it, which then becomes free in the bloodstream. Effectively, the concentration of the first medication is now larger, so more of it reaches the brain, with potentially toxic results. 

TOLBUTAMIDE FIBRATES Fibrates may t efficacy of sulphonylureas Uncertain postulated that fibrates displace sulphonylureas from plasma proteins and l their hepatic metabolism. In addition, fenofibrate may inhibit CYP2C9-mediated metabolism of tolbutamide Monitor blood glucose levels closely. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

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