C
PARAMETERS
volume of distribution
(Vd)
2. Half life
3. Clearance
1.
VOLUME OF
DISTRIBUTION
V <V
app
real
And lie between blood volume and total body water that
is between 6 to 42 liters
drugs which bind selectively to extra vascular tissue
e.g., CHLOROQUINE
V > V
app
real
Drugs
Vd lit/70 kg
heparin
digioxin
420
Mathematical formula :
1.
Case 1 :
plasma
120mg in body
20 mg/ml in
plasma
= 6 liter
Case 2:
120 mg in body
1 mg/ml in
plasma
=120 liter
Low Vd
High drug in plasma
high Vd
Low drug in plasma
Vd = dose
Cp
3. if we want to calculate the volume
of distribution at the elimination
phase then we consider the following
graph.
Vd = Co
Cp
CLEARANCE
volume
So ;
Rate of elimination = clearance * concentration
mass / time
volume / time
mass/volume
Zero order
kinetics
clearance
clearance =
Vd
constant )
volume /time
volume
1/ time
K el = cl/Vd
Total clearance
Cl
tatal
tot
* Cp
Organ clearance
The
is
Extraction
Flow
now,
Organ
clearance =
Where as
the rate of drug entering the organ = blood flow in artery* conc of drug in plasma
The rate of drug leaving the organ = blood flow in vein* cinc of drug in plasma
For
every drug, each organ of elimination has its own clearance (e.g.
hepatic clearance,renal clearance). The total body clearance results from the addition
of these clearances:
CL=Renal CL+Hepatic CL+ other CL
Mathematically
renal clearance
that is the rate of drug passing through the kidney is equal to the
drug excreted by the kidney
Renal
Hepatic clearance
volume of the body fluid cleared of drug per unit of time via
liver
hepatic clearance depend upon
1. hepatic blood flow (e.g. congestive heart failure)
2. plasma protein binding (e.g. hypoalbuminemia,
displacement by other drugs)
3. hepatic enzymatic activity (e.g. liver failure, specific
inhibition or induction by drugs, genetic polymorphism) also
reffered to as intrinsic activity of liver
. Whlie taking about the hepatic clearance a term is
INTRNISIC HEPATIC CLEARANCE , it is the ability of liver to
remove the drug from the body fluid in the absence of
other suppressing factors.(blodd flow and protein binding)
Mathematically
CLH =
Qcpa Qcpv
Cpa
= Q (cpa cpv))
cpa
CONC OF DRUG
HALF LIFE
INTRODUCTION :
A
drug half life is the time it takes for half of the given
dose to b eliminated from the body or bloodstream
there are two types of half lives
1. BIOLOGICAL OR ELIMINATION HALF LIFE is the time
it takes for the bioactivity of the drug to reduce by 50%
of its initial value
2. PLASMA HALF LIFE is the takes it takes for the
concentration of the drug in the blood stream to reduce
by 50%
. We at this point are more concerned with
PLASMA HALF LIFE
. Plasma half life is the time measurement which starts
when the drug reaches equilibrium that is equal
amount of the drug is at administration site and
in the blood circulation or it is fully absorbed
There
No of half life
1 x life
50
2 x life
75
25
3 x life
87.5
12.5
4 x life
93.75
6.25
5 x life
96.87
3.13
Eliminati
on rate
= chnge
( mg/lit) in
Cp/chan
ge in
time
8-4 /1 =4
4-2/1= 2
2-1/1= 1
1-
Time
(hr)
Plasma
con
(mg/ml)
Eliminat
ion rate
= chnge
in
cp/chng
e in
time
Some
Zero
order
Cp
1st
order
Time
Mathematically
half life = 0.693 / Kel
This reflects that the elimination half life is inversely
poportional to rate of elimination
More the rate of elimination lesser will be the stay of drug
with in the body and thus shorter will be the half life and
vice versa .
Interrelationship of the
three parameters
t = o.693/ Kel
And ,
Kel = clearance /Vd
So ,
t
= o.693 Vd / clearance