REPEATED ADMINISTRATION OF AN INHIBITOR 



423 



This is the same time as is required for the concentration after a single 

 dose to fall to 10% of (I)o. It is interesting that ^0.9 does not depend on how 

 frequently the inhibitor is administered; the shorter the interval be- 

 tween doses, the more must be given, but the total time required is the same. 

 The rise in concentration with the number of administrations and with 



TIME 



Fig. 8-8. Changes in the internal inhibitor concentration during repeated intrave- 

 nous administrations in an animal. At = 10 and k — 0.1. The final concentrations 

 reached after approximately five administrations are {^)min — ^-^l nail/ and 



(I)„„^ = 15.81 milf . 



the time is plotted in Fig. 8-9 for different intervals between doses. The very 

 high inhibitor concentrations reached with frequent administrations are evi- 

 dent. Likewise, for a constant dosage interval, the slower the disappear- 

 ance of the inhibitor (the smaller k), the higher the final level reached. 

 If the inhibitor is tightly bound to the tissues, continuous administration 

 can result in very high total concentrations, but the concentration of free 

 inhibitor in solution may not rise greatly and the inhibition on a parti- 

 cular enzyme need not follow the total concentration of inhibitor. 



The value of such a quantitative formulation of accumulation is that it 

 can aid in the rational planning of experimental procedures. If a constant 



