     ## Clearance, CL

At this point we can define another pharmacokinetic parameter, clearance. Clearance can be defined as the volume of plasma which is completely cleared of drug per unit time. The symbol is CL and the units are ml/min, L/hr, i.e. volume per time. Another way of looking at Clearance is to consider the drug being eliminated from the body ONLY via the kidneys. [If we were to also assume that all of the drug that reaches the kidneys is removed from the plasma then we have a situation where the clearance of the drug is equal to the plasma flow rate to the kidneys. All of the plasma reaching the kidneys would be cleared of drug.]

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.

Homework Set 1997 [Answers in Excel format]     