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PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

Clinical Significance

1. Drug displacement interactions:

› Drug displacement interactions occur between two or more drugs that bind to same

plasma protein site.

› When two drugs are given, each with a high affinity for plasma protein, they

compete for the available binding sites.

› If one drug is binding to such a site, then administration of second drug having

higher affinity for the same site results in displacement of first drug from its

binding site.

› In some instances, a slight displacement of a drug will result in marked increase

in its biological activity.

Examples

 Ex 1: Administration of phenylbutazone to a patient on warfarin therapy results

in displacement of warfarin from its binding site.

Warfarin:

 Has high plasma protein binding of about 99% (free drug concentration = 1%),

 Shows a small volume of distribution (remains confined to blood compartments)
and

 Has a narrow therapeutic index.
 If just 1% of warfarin is displaced by the phenylbutazone, the concentration of

free warfarin will be doubled (2%).

 The enhanced concentration of free warfarin may cause severe haemorrhagic

episodes, which may result in lethality.

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