Estimation of systemic clearance

Total clearance (Ch) can be derived as follows. From an earlier definition, we know that  

The renal clearance of a drug may be determined by employing any of the following methods. 

Ku is the excretion rate constant (h ) and V is the apparent volume of distribution (e.g. mL, Lkg body weight). 

Equations 4.19 and 4.20 are equivalent since the product of percentage excreted in unchanged form multiplied by the dose administered (i.e. the numerator of the right-hand side of Eq. 4.20) provides the amount of drug excreted in unchanged form in urine at time infinity (XJ.., the numerator value of the right-hand side of Eq. 4.19). 

This relationship makes it relatively easy to determine the renal clearance (Clr) of any drug that is excreted, to some measurable extent, in unchanged form in the urine  

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The estimation of systemic clearance together with this value gives valuable information about the behaviour of a drug. High clearance drugs with values approaching hepatic blood flow will indicate hepatic extraction (metabolism) as a reason for low bioavailability. In contrast poor absorption will probably be the problem in low clearance drugs which show low bioavailabilities. 

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