Answer to Practice Problem #8 Dose- and Time-Dependent Pharmacokinetics Tutorial:

 

Since phenylbutazone is a low clearance drug (which you should remember from the list of low clearance drugs given in the Hepatic Clearance lectures), the clearance of such a drug is given as

 

CL_H ~ f_ubCL_uint

 

As time after the dose progresses, the metabolite of phenylbutazone will accumulate (since the half-life of the metabolite is longer than that of the parent compound, which we know since it exhibits elimination rate-limited elimination). Since this metabolite inhibits the metabolism of phenylbutazone, the CL_uint will decrease as the metabolite accumulates, resulting in a decrease in the CL_T. This results in a relationship as shown below:

 

 

 

 

 

 

Last revised 07/14/05

 

ã 2005 -  Craig K. Svensson, Pharm.D., Ph.D.

 

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