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PRESENTATION BY

RAVULAPALLI CHIRANJEEVI
1
ST
M.Pharmacy(Pharmaceutics)
Vikas college of Pharmacy







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Concept of clearance
Renal Clearance
Factors affecting renal excretion or renal clearance
Organ clearance
Hepatic clearance



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CONCEPT OF CLEARANCE

The clearance concept was first introduced to describe renal excretion of
endogenous compounds in order to measure the kidney function.
The clearence applied to all organs involved in drug elimination such as
liver ,lungs, the biliary system and refer to as hepatic clearence, pulmonary
clearence.

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.
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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.
Clearance (Cl) = Elimination rate
Plasma drug concentration



dX/dt
Cl = ------------
C

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TOTAL BODY CLEARENCE
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Elimination of a drug from the body involes process occuring inkidney,liver,lungs
and other eliminating orgns.
It can be estimated by dividing the rate of elimination by each organ with the
concentration of drug thus
HEPATIC CLEARENCE
Cl
H
= rate of elimination by liver
C

RENAL CLEARENCE
Cl
R
= rate of elimnination by kidney
C


Clothers = rate of elimination by other organs
C
TOTAL BODY CLEARENCE
Cl
T
= Cl
R
+ Cl
H
+ Clothers
According to earlier definition

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dX/dt
CI
T
=
--------------

C

K
E
X
CI
T
=
--------------

C

CI
T
=

K
E
.

V
d




CI
T
= 0.693.

V
d

/

t
1/2

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Organ Clearance: The best way of understanding clearance is at
individual organ level.
Such a physiologic approach is advantageous in predicting and
evaluating the influence of pathology, blood flow, P-D binding, enzyme
activity, etc. on drug elimination.

At an organ level, the rate of elimination can be written as:
Rate of elimination by an organ = Rate of presentation to the organ
- Rate of exit from the organ

Rate of presentation = Organ blood flow Entering concentration
(input) = Q. C
in

Rate of exit (output) = Organ blood flow Exiting concentration
= Q. C
out
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Rate of elimination = Q.C
in
- Q,C
out

(also called as rate of extraction) = Q (C
in
C
out
)

Division of above equation by concentration of drug that enters the organ of
elimination C
in
yields an expression for clearance of drug by the organ under
consideration. Thus:

Rate of extraction = Cl
organ
= Q (C
in
C
out
) = Q.ER
C
in
C
in


where, ER = (C
in
- C
out
)/C
in
is called as extraction ratio
It has no units and its value ranges from zero (no elimination) to one (complete
elimination).
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Based on ER values, drugs can be classified into 3 groups:
-drugs with high ER (above 0.7)
-drugs with intermediate ER (between 0.7 to 0.3) and
-drugs with low ER (below 0.3).

ER is an index of how efficiently the eliminating organ clears the blood flowing through it of
drug.
F = 1-ER
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Hepatic Clearance:

For certain drugs, the nonrenal clearance can be assumed as equal to hepatic clearance CI
H
. It
is given as:

CI
H
= CI
T
- CI
R


An equation parallel to equation can also be written for hepatic clearance:

CI
H
= Q
H
.ER
H

where, Q
H
= hepatic blood flow (about 1.5 liters/min), and

ER
H
= hepatic extraction ratio.

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The hepatic clearance of the drugs can be divided into two groups
1.Drugs with hepatic blood flow rate-limited clearance
2.Drugs with intrinsic capacity limited clearance


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1.Drugs with hepatic blood flow rate-limited clearance:
When ER
H
is one, Cl
H
approaches its maximum value i.e.hepatic blood flow in
such situation,hepatic clearance is said to be perfusion rate limited.Alteration in
hepatic blood flow significantly affects the elimination of drugs with high ER
H

eg;:propranolol,lidocaine,such drugs are removed from the blood as rapidly as they are
presented to the liver.Indocyanine green is so rapidly eliminated by human liver that
its clearance is often used as an indicator of hepatic blood flow rate.

F=1- ER
H=
AUC
oral





AUC
I.V.

Intrinsic capacity clearance: Denoted as ,it is defined as the inherent ability of
an organ to irreversibly remove a drug in the absence of any flow
limitations.Its depends upon the hepatic enzyme activity.
Drugs with low and with elimination by metabolism are greatly
affected by changes in enzyme activity.Hepatic clearance of such drugs are said
to be capacity limited.Eg:theophylline.
Hepatic clearance of the drugs with low ER is independent of blood
flow rate but sensitivity to changes in protein binding.
HEPATIC AND RENAL EXTRACTION RATIO OF SOME DRUGS AND METABOLITES:
EXTRACTION RATIO:


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High Intermediate Low
Hepatic
extraction
Propranolol
Lidocaine
Nitrro
glycerine
Aspirin
Codeine
Quinidine

Diazepam
Phenobarbit
ol
phenytoin
Renal
extraction
Some
penicillins,sev
eral sulphates
Procainamide,
cimetidine
Digoxin
Atenolol
tetracycline
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Renal Clearance (CI
R
): 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:
CI
R
= Rate of urinary excretion
Plasma drug concentration
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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".

CI
R
= Rate of filtration + Rate of secretion - Rate of reabsorption
C
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Factors affecting renal excretion or renal clearance

1. Physicochemical properties of the drug.Eg:molecular size,pka
2. Plasma concentration of the drug.
3. Distribution and binding characteristics of the drug
4. Urine pH
5. Blood flow to the kidneys
6. Biological factors
7. Drug interactions

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Physicochemical Properties of the Drug
Important physicochemical factors affecting renal excretion of a drug are -
molecular size, pK
a
and lipid solubility.

Plasma Concentration of the Drug
1.Drug excreted by filtretion only
2.Drug filtered and actively reabsorbed
3.Drug filtered as well actively secreted
Plasma Concentration
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REFERENCE:
Biopharmaceutics and pharmacokinetics
D.M.BRAHMANKAR
SUNIL B. JAISWAL
Biopharmaceutics and clinical pharmacokinetics
MILO GIBALDI
Applied biopharmaceutics and pharmacokinetics
LEON SHARGEL
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I THANK TO BELOWED STAFF AND
MY ROOM MATES
BE PROUD TO BE A
PHARMACIST
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