Concept of Clearance

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Chapter: Biopharmaceutics and Pharmacokinetics : Excretion of Drugs

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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