ONE

COMPARTMENT
OPEN MODEL

S.Sangeetha., M.PHARM., (Ph.d)

Department of Pharmaceutics
SRM College of Pharmacy
1
SRM University
 ONE COMPARTMENT OPEN MODEL
(Instantaneous distribution model)
‐The body is considered as a single, kinetically
homogeneous unit.
-This model applies only to those drugs that
distributes rapidly throughout the body.
-Drugs move dynamically in an out of this
compartment
-Elimination is first order(monoexponential)
process with first order rate constant.
-Rate of input(absorption)> rate of output
(elimination)

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¾Depending on rate of input, several one 
compartment open models are :
1. one compartment open model, i.v. bolus
administration
2. one compartment open model , continuous i.v.
infusion .
3. one compartment open model, e.v.
administration, zero order absorption.
4. one compartment open model, e.v.
administration, first order absorption

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INTRAVENOUS  BOLUS  ADMINISTRATION 
When  drug is given in the form of rapid i.v. injection it takes about  one to three 
Minutes for complete circulation and therefore the rate of absorption is neglected

dX = Rate In – Rate Out

dt
dX = - Rate Out KE =first order elimination rate constant
dt X= amt of drug in body at any time t
dX = - KEX remaining in the body
dt
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¾Estimation of pharmacokinetic parameters
Elimination rate constant:
dX = - KEX
dt

Integrating above equation  yields
ln X = ln X0 – KEt
where Xo = amount of drug at time t=0

Equation can be written in exponential form as

X= Xo e‐Ket  
Transforming equation into logarithm form we get,
Log X =  Log X0   ‐ KEt
2.303
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, KE   =   

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 Elimination half life:
It is defined as time taken for the amount of drug in the
body as well as plasma concentration to decline by ½ or 50
% its initial value.
It is expressed in hrs or mins
t1/2 = 0.693  
KE

Half life is secondary parameter that depends upon the

primary parameters clearance and volume of distribution
according to following equation,
t1/2 = 0.693 Vd
ClT

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 Apparent volume of distribution:
Vd = amt of drug in the body/ plasma drug conc.
or Vd = X/C
For drugs given as i.v. bolus ,
Vd  =    X0
KE AUC

For drugs administered extravascularly,
Vd =    F   X0
KE AUC          where,X0 = dose administered
F = fraction of drug absorbed in
systemic circulation.  

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 Clearance
Clearance is defined as the theoritical volume of body
fluid containing drug from which the drug is completely
removed in a given period of time.
ClT =         Rate of elimination
Plasma drug concentration
Cl =          dX / dt (dx/dt = KE.X)

C          
ClT =          KE Vd   
ClT =           X0
AUC       
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Total body clearance :
It is estimated by dividing the rate of elimination by
each organ with the concentration of drug presented
to it.
Renal clearance
ClR = rate of elimination by kidney
C
Hepatic clearance
ClH = rate of elimination by liver
C
Thus , ClT is also called as total systemic clearance ,
is an additive property of individual organ clearances.
It is represented as:
ClT = ClR + ClH+ Cl others

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 ORGAN CLEARANCE
• Rate of Elimination = Rate of Presentation – Rate of
by an organ to organ (input) exit from
organ

Rate of elimination      =      Q. C in  ‐ Q. C out
(Rate of extraction)
Extraction   Ratio     ER =         ( Cin – Cout)
Cin
ER is an index of how efficiently the eliminating organ clears
the blood flowing through it of drug.
Based on ER values drugs can be classified as:
• Drugs with high ER = above 0.7
• Drugs with intermediate ER = between 0.7‐ 0.3                                       
• Drugs with low ER = below 0.3 
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 Intravenous Infusion:
Rapid i.v. injection is unsuitable when the drug has
potential to precipitate toxicity or when maintenance of a
stable concentration or amount of the drug in body is
desired. In such a situation , the drug is administered at a
constant rate (zero ordered) by i.v. infusion.
Advantages of zero order infusion of drug include
1. Ease of control of rate of infusion.
2. Prevents fluctuating maxima and minima plasma level.
This is desired especially when the drug has a narrow
therapeutic index.
3. Other drugs , electrolytes and nutrients can be
conveniently administered simultaneously by the same
infusion line in critically ill patients.

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 At any time during infusion , the rate of change in amt.
of drug in the body , dx/dt is the difference between
the zero order rate of drug infusion Ro and first order
rate elimination , ‐KE x:
dX = R0‐ KEX , by integrating the equation  ,
dt

x = Ro (1-e-kE t) ,
kE

Since, x=vdc the above equation can be transformed in

to concentration terms ,

C= Ro (1-e-kE t) = Ro (1-e-kE t)
kEvd clT
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At the start of constant rate infusion , the amt. of drug in the body zero and
hence , there is no elimination. As time passes , the amt. of the drug in the
body rises gradually until a point after which the rate of the elimination equals
the rate of infusion i.e. the concentration of drug in plasma approaches a
constant value called as steady-state.

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At steady state , the rate of change in amt. of drug in
body is zero , hence
zero=RO-KE XSS
KEXSS = RO , Transforming to concentration terms and
rearranging the equation ,
Css= Ro = Ro
KEvd ClT
Where , XSS and Css are the amt. of the drug in body
and concentration of the drug in plasma at steady state
respectively.
The value of KE can be obtain from the slope of straight
line obtained after a semi logarithmic plot log c vs. time.
By substituting the R0/ClT=CSS ,
C=CSS(1 – e-KEt)
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Rearrangement yields

Transforming into log form.

A semilog plot of (Css – C)/Css versus t results in a straight line with slope –
KE /2.303

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Infusion plus loading dose:
It takes very long time for the drugs having longer half
lives before the steady state concentration is reached.

An i.v. loading dose is given to yield the desired steady-

state immediately upon injection prior to starting the
infusion.

It should then be followed immediately by i.v. infusion at a

rate enough to maintain this concentration.

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The equation for the plasma concentration time profile
following i.v. loading dose and constant rate i.v. infusion,

C =X0,L e-kEt + R0 (1- e-Ket)

Vd KEVd

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 One Compartment open model
™ EXTRAVASCULAR ADMINISTRATION
When drug is administered by extravascular route,
absorption is prerequisite for its therapeutic activity. The
rate of absorption may be described mathematically as
zero-order or first-order process.
After e.v. administration, the rate of change in the amount
of drug in the body is given by
dx = Rate of absorption – Rate of elimination
dt
dX = dXev - dxe
dt dt dt

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• During absorption phase, the rate of absorption is
greater than elimination phase.
dXev > dxe
dt dt

• At peak plasma concentration,

dXev = dxe
dt dt

• During post absorption phase,

dXev < dxe
dt dt

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ZERO-ORDER ABSORPTION MODEL
R0 KE
Drug Blood Excretion

This model similar to that of constant rate infusion and

all equation which applies to it are applicable to this
model.

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FIRST-ORDER ABSORPTION MODEL
Ka KE
Drug Blood Excretion
first order
From equ. dX = dXev - dxe
dt dt dt
Differentiating above equ. We get,
dX = Ka Xa – KEX, Ka= absorption rate const.
dt Xa= amt of drug remaining
to be absorbed.
Integrating above equ.,

X= K a FX o
(K a − K E )
[
e − K ET − e − K at ]

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ABSORPTION RATE CONSTANT
This can be calculated by METHOD OF RESIDUALS.
Method is also known as Feathering, stripping and
peeling.
Drug that folllows one- compartment kinetics and
administered e.v. , the concentration of drug in plasma
is expressed by biexponential equation:

Assuming A = Log Ka F X 0
Vd (Ka – KE)

C = A e-kEt – A e-Kat

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 During the elimination phase, when absorption is most
over, Ka >>KE

C = A e-Ket
In log form above equation is

Log C = Log A - Ket

2.303

Where, C = back extraplotted plasma conc. Values.

Substracting true plasma conc. From extraploted one,

log(C – C ) =Cδ = Log A - Ket

2.303

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This method works best when difference between Ka
KE is large (Ka/KE >3)

If KE/Ka > 3 , the terminal slope estimates Ka and not

KE whereas the slope of residuals line gives Ke and not
Ka.

This is called as flip-flop phenomenon since the slopes

of the two lines have exchanged their meanings.

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Wagner Nelson Method for Estimation of Ka
The method involves determination of ka from percent un absorbed- time
plots and does not required assumption of zero or first- order absorption

After oral administration of single dose of drug at any given time ,the amount
of drug in the body X and the amount of drug eliminated from the body XE
.Thus:

X=VdC ,

The total amount of drug absorbed into systemic circulation from time zero to
infinite can be given as :

Since at t = ∞, ,the above equation reduce to :

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The fraction of drug absorbed at any time t is given as:

Percent drug unabsorbed at any time is therefore:

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References:
1. D.M. Brahmankar, compartment model in
Biopharmaceutics and Pharmacokinetics, Vallabh
prakashan, second editon, 2009; p:

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