Protein binding

Protein binding in blood
Drugs sometimes bind to circulating proteins. When a drug is protein bound it is usually not free to bind to its intended receptor or be cleared by the clearing organ (shown in the illustration as the liver). In cases of severe liver dysfunction, the amount of albumin available for binding can be decreased, allowing for a larger free fraction of drug. However, this does not always mean a larger effect at the receptors, as more free drug is also being presented to the clearing organs for drug elimination. Another drug-binding protein is alpha1-acid glycoprotein. The concentrations of this protein can increase significantly after traumas such as an MI or a serious burn. Some examples of % protein binding include: 10% gentamicin; 17% caffeine; 50% penicillin G; 90% phenytoin; 99% warfarin. See how protein binding affects drug concentrations by clicking 
here. Drug interactions usually are the biggest concern with regard to protein binding. However, the interactions are relevant only for drugs highly bound to proteins. Example: Drug 1:99% protein boundFraction unbound= 1+ Drug XBinds to protein: competitionDrug1: 99% >> 98% protein bindingFraction unbound: 1% >> 2% 100% increase of active drug Drug 2:99.9% protein bound Fraction unbound= 0.1% + Drug X Binds to protein: competition Drug2: 99.9% >> 98.9% protein binding Fraction unbound: 0.1% >> 1.1% 1100% increase of active drug    

Warfarin is a Vitamin K antagonist (anticoagulant) that is characterized by 97% protein-binding in plasma. What happens to the effect of warfarin when another drug is given that is also highly bound to the same protein in plasma?