Clearance Rate as an Expression of Drug Elimination Rate

Another method aside from renal excretion by which drugs are cleared from the body is through metabolism.  However, it is not possible to measure directly the amount cleared by metabolism.  Calculation of the total clearance rate (TCR), or total body clearance, can be made from its pharmacokinetic parameters utilizing this equation:

TCR = kelVd

EXAMPLE 2:  Procaine's biological half-life within a patient is 30 minutes and its volume of distribution is approximately 60 liters. Calculate the TCR of procaine.

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When metabolism and urinary excretion both occur in the excretion of a drug, it is possible to calculate the metabolic clearance rate (MCR) by taking the difference of TCR and RCR:

MCR = TCR - RCR

Alternatively, the RCR and MCR can be calculated by using the following formulas.  RCR can be obtained by multiplying the TCR by the fraction of the dose excreted unchanged into urine, fe:

RCR = feTCR

And if we can assume that the fraction of the dose not appearing unchanged in the urine has been metabolized, the MCR is just:

MCR = (1-fe)TCR 

EXAMPLE 3:  Sulfadiazine has a biological half-life of 19hr in a patient and a volume of distribution of 13 liters.   Sixty percent of the dose was recovered as unchanged drug in urine.  Calculate TCR, RCR, and MCR for sulfadiazine in the person.

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In this section, we have assumed that there are only two means by which drugs are eliminated from the body. This assumption, we should note, is incorrect since drugs not appearing unchanged in the urine but are eliminated unchanged in feces are assumed to have been metabolized. The values for clearance rates are greatly affected by this assumption. 

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