UNIT 3

One compartment model

Extra vascular administration

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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 follows 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. 9
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:
2.N Venkateswarulu, Biopharmaceutics and pharmacokinetics, Saltan Bazar,
Hyderabad : PharmaMed Press, ©2008.

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