Concept of Clearance
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The clearance concept was first introduced to describe renal excretion of endogenous compounds in order to measure the kidney function.
CONCEPT OF CLEARANCE
The clearance concept was first introduced to
describe renal excretion of endogenous compounds in order to measure the kidney
function. The term is now applied to all organs involved in drug elimination
such as liver, lungs, the biliary system, etc. and referred to as hepatic
clearance, pulmonary clearance, biliary clearance and so on. The sum of individual clearances by all eliminating organs is
called as total body clearance or
total systemic clearance.
It is sometimes expressed as a sum of renal clearance and nonrenal clearance.
Clearance is defined as the hypothetical volume of body fluids containing drug
from which the drug is removed or
cleared completely in a specific period of time. It is expressed in ml/min
and is a constant for any given plasma drug concentration. In comparison to
apparent volume of distribution which relates plasma drug concentration to the
amount of drug in the body, clearance relates plasma concentration to the rate
of drug elimination.
Clearance (Cl) = Elimination rate / Plasma drug concentration (6.9)
Renal Clearance (ClR): It can be defined as the volume of blood or plasma
which is completely cleared of the unchanged drug by the kidney per unit time. It is expressed mathematically
as:
ClR = Rate of urinary excretion / Plasma drug concentration (6.10)
Physiologically speaking, renal clearance is the ratio
of “sum of rate of glomerular filtration
and active secretion minus rate of reabsorption” to “plasma drug concentration C”.
ClR = [ Rate of filtration + Rate of
secretion- Rate of reabsorption ] / C (6.11)
TABLE 6.2
Relationship between Renal Clearance Values and Mechanism of Clearance
The contribution of each of the above physiologic
processes in clearing a drug cannot be determined by direct measurement. It can
however be determined by comparing the clearance values obtained for a drug
with that of an agent such as creatinine or inulin which is cleared by
glomerular filtration only. The ratio of these two values is called as renal clearance ratio or excretion
ratio.
Renal Clearance Ratio = ClR of drug / ClR
of creatinine (6.12)
Thus, depending upon whether the drug is only
filtered, filtered and secreted or filtered and reabsorbed, the clearance ratio
will vary (Table 6.2.). The renal clearance values range from zero to 650
ml/min and the clearance ratio from zero to five.
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