The amount cleared by the body per unit time is dU/dt, the rate of elimination (also the rate of excretion in this example). To calculate the volume which contains that amount we can divide by Cp. That is the volume = amount/concentration. Thus:-
Equation V-17. Clearance as the Ratio between Rate of Excretion and Cp
Equation V-18. Clearance calculated from kel and V
As we have defined the term here it is the total body clearance. We have considered that the drug is cleared totally by excretion in urine. Below we will see that the total body clearance can be divided into a clearance due to renal excretion and that due to metabolism.
Clearance is a useful term when talking of drug elimination since it can be related to the efficiency of the organs of elimination and blood flow to the organ of elimination. It is useful in investigating mechanisms of elimination and renal or hepatic function in cases of reduced clearance of test substances. Also the units of clearance, volume/time (e.g. ml/min) are easier to visualize, compared with elimination rate constant (units 1/time, e.g. 1/hr).
Diagram V-3 Representation of Renal Clearance
Total body clearance, CL, can be separated into clearance due to renal elimination, CLr and clearance due to metabolism, CLm.
CLr = ke * V (renal clearance)
and
CLm = km * V (metabolic clearance)
NOTE
CL = CLr + CLm
ANOTHER METHOD of calculating CL can be derived
Integrating
gives
thus
Equation V-19. Renal Clearance calculated from U
and AUC
also
Equation V-20. Metabolic Clearance calculated from M and AUC
and
Equation V-21. Clearance calculated from Dose and AUC
This equation uses the DATA only (without fitting a line through the data or modeling the data) using the trapezoidal rule. Thus this is a model independent method.
From Equation V-17
thus a plot of dU/dt versus Cp will give a straight line through the origin with a slope equal to the clearance, CL.