The effect of tissue-binding interactions

Up to this point, the discussion has centered on the changes caused by binding of drug by proteins in the plasma. That is, changes in pharmacokinetic parameters caused by a change in the fraction drug unbound in the plasma have been discussed. 

Using the equations generated above, changes in pharmacokinetic parameters occasioned by a changes in the fraction unbound in the tissues can be examined. 

The apparent volume of distribution at steady state is given by the general equation, Eq. 16.8  

In the case of drugs with a large volume of distribution, the ratio of the fraction of drug unbound in the plasma to the fraction unbound in the tissues fupifut) is large and the full equation (Eq. 16.8) must be used, in which case an increase in the fraction unbound in tissue will cause an almost proportional decrease in the volume of distribution at steady state. 

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