FATE OF INHIBITORS IN THE ANIMAL 



419 



sues will delay the eventual inactivation or excretion. Finally, the enzyme 

 inhibition itself need not follow the level of (I,), since the rate of combi- 

 nation of the inhibitor with the enzyme may be slow or the reversi- 

 bility of the inhibition may be the limiting factor. However, these and 

 other factors, when known, can be superimposed on the basic behavior ex- 

 pressed by the equations derived here. The important concepts to be gain- 

 ed by a study of these equations relate to the dependence of intracellular 

 inhibitor concentration on the relative rates of the fundamental processes 



TIME — ^ 



Fig. 8-6. Variation of intracellular inhibitor concentration with time in an organ- 

 ism in which the inhibitor is excreted as well as destroyed in the tissues. (Io)o = 10 

 mM and k^ = k^ = I. Curve 1: no excretion (Eq. 8-9); curve 2: excretion with 

 k„ = 1 (Eq. 8-16); curve 3: excretion with k^ = 3 (Eq. 8-16). 



that are involved, namely the rate of uptake, the rate of inactivation, and 

 the rate of excretion. 



If the inhibitor is metabolized to another compound in the body and 

 both the inhibitor and its metabolic product are excreted from the body, 

 the concentration of each is determined by the rate constants of the meta- 

 bolic process and the excretion. This problem was treated by Nelson and 

 0' Reilly (1960) and applied to the behavior of sulfisoxazole in the human. 



