All drugs in the body are to some extent bound to protein. Protein binding becomes important where a high percentage of the drug is bound - for example in warfarin, phenytoin and tolbutamide. Ordinarily, altering the binding will change the unbound amount and thus change the effect the drug is having. Usually binding only changes a small amount, and also the drug may be soaked up by tissues.
To take the example of phenytoin, and the interpretation of measurements of plasma concentration, normally there is a total of 60 micromoles per litre with 10% unbound. If protein binding is reduced, increasing the free fraction to 20%, the free concentration has actually doubled, and the increased free fraction - not concentration - leads to increased rate of clearence, and the plasma concentration will drop to 30 micromols per litre. The message here is - look at the patient, not the plasma concentration.
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