## 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]
Homework Set 1995

This page was last modified: 12 February 2001
Copyright 2001 David W.A. Bourne