Multicompartment Models

Biopharmaceutics

1. MULTICOMPARTMENT MODELS
Prepared By
GirijeshKumar Pandey
M.Pharm. (Pharmaceutics)

2. Contents
•Introduction
•Two-Compartment Open model
•Intravenous bolus administration
•Intravenous Infusion
•Extra vascular administration
•Conclusion
•References

3. Introduction
•One compartment is described by mono-
exponential term i.e. elimination.
•For large class of drugs this terms is not sufficient
to describe its disposition.
•It needs a bi-or multi-exponential terms
•The body is composed of a heterogeneous group
of tissues each with different degree of blood
flow and affinity for drug and therefore different
rates of elimination.
•Multi-compartment characteristics are best
described by administration as i.v. bolus.

4. Two Compartment Model
•The simplest and commonest is the two compartment
model which classifies the body tissues in two
categories :
1) Central compartment or Compartment 1
2) Peripheral or Tissue Compartment or Compartment 2.
•Compartment 1 comprises of blood and highly
perfusedtissues like liver, lungs, kidneys, etc.
•Elimination usually occurs from this compartment.
•Compartment 2 comprises of poorly perfusedand slow
equilibriatingtissues such as muscles, skin, adipose,
etc.

5. Two Compartment Model
•General Grouping of Tissue According to Blood
Supply

6. Two Compartment Model
•Depending upon the compartment from
which the drug is eliminated, the 2
compartment model can be further
categorised into :
-With elimination from Central compartment
-With elimination from peripheral
compartment
-With elimination from both the
compartments

7. Two Compartment Model

8. Two compartment Open model-
I.V. bolus administration:
•Elimination from central compartment
1 Central 2 Peripheral
•After the iv bolus of a drug the decline in the
plasma conc. is bi-exponential.
•Two disposition processes-distribution and
elimination.
•These two processes are only evident when a
semilogplot of C vst is made.

9. Two compartment Open model-
I.V. bolus administration:
•Model Structure for Two Compartment Model

10. Two compartment Open model-
I.V. bolus administration:
•Where, X 0 = IV bolus dose administered
C c= X 1 = amount of drug in the central compartment
C p = X 2 = amount of drug in the peripheral compartment
k 12 = rate constant for transfer of drug from the central to the
peripheral compartment
k 21 = rate constant for transfer of drug from the peripheral to
the central compartment
k E = first order elimination rate constant.
Elimination of drug out of the central compartment

11. Two compartment Open model-
I.V. bolus administration:
•The second, slower rate process, is called as the post-
distributive or elimination phase.
•In contrast to central compartment, the concof drug in
the peripheral compartment first increases and reaches
its max.
•The Rate change in drug conc. in the central
compartment is given by,
•Extending the relationship X= V d C
•Where, V c and V p = apparent volumes of C1 and C2

12. Two compartment Open model-
I.V. bolus administration:
•The rate of change in drug concin the
peripheral component is given by:
•On integration equation gives conc. of drug in
central and peripheral compartments at given
time t :

13. Two Compartment Open Model –
Intravenous Infusion
•The plasma or central compartment concof a
drug when administered as constant rate (0
order) i.v. infusion is given as:

14. Two Compartment Open Model –
Intravenous Infusion
•At steady state the second and the third term
in the bracket becomes zero and the equation
reduces to: Now, The loading dose

15. Two-Compartment Open Model-
Extravascularadministration
•First -Order Absorption
•The model can be depicted as follows :
•The rate of change in drug conc. in the central
compartment is described by three exponents :
An absorption exponent, and
•Two usual exponents that describe drug
disposition.

16. Two-Compartment Open Model-
Extravascularadministration
•The plasma concat time t is,
•Where, L, M & N are coefficients

17. Conclusion
•The future should involve the use of models
capable of incorporating physico-chemical data
and biological information .
•Compartment modelling is useful in Characterize
the behaviorof drug in patient, predicting conc.
of drug in various body fluids with dosage
regimen , calculating optimum dosage regimen
for individual patient, evaluating bioequivalence
between different formulation, explaining drug
interaction.

18. References
•D.M.Brahmankar& S.B. Jaiswal, Biopharmaceutics&
pharmacokinetics. A.treatise, First edition, Vallabh
Prakashan, P.No. 290-299,
•Leuand febiger, Biopharmaceutics& clinical
pharmacokinetics by Milo Giberldi, Fourth edition,
Philadelphis, 1991. P.No. 213-230.
•Leon shargeland Andrew Yu, A ppliedBiopharmaceutics
and pharmacokinetics, Fourth edition.page no. 47-62.
•Milo Gibaldi, Biopharmaceuticsand clinical
pharmacokinetics Fourth edition .page no.14-23,
•http://www.authorstream.com/Presentation/abhijit_26-
1830737-multi-compartment-models/