dose regimen two compartment

1. Department of pharmaceutical sciences
Dr. Hari Singh Gour Vishwavidyalaya
Sagar, (M.P.)
(A CENTRAL UNIVERSITY)
PRESENTED BY
Anshul Vishwakarma
Y21254007
Kinetic of multiple dosing:-Two compartment models

2. CONTENT
• Dosage regimen
• Multiple dosage regimen
• Method of residuals
• Two-compartment open model extravascular administration
• Two-compartment open model intravenous infusion
• References

3. Dosage regimen
Objective of dosage regimen
The overall objective of dosage regimen design is to achieve a target drug concentration at
the receptor site

4. Multipledosage regimen
• When the duration of treatment
of disease is smaller than the
therapeutic activity of drug,
single dose are given .
• When the duration of treatment
of disease is larger than the
therapeutic effect of drug,
multiple dosage regimen are
given.

5. TWO-COMPARTMENT OPEN MODEL
• Many drugs given in a single intravenous bolus dose demonstrate a plasma level–time
curve that does not decline as a single exponential (first-order) process.
• The plasma level–time curve for a drug that follows a two-compartment model shows that
the plasma drug concentration declines biexponentially as the sum of two first- order
processes - distribution and elimination.

6. • In this model, the drug distributes into two compartments:
 Central compartment: these highly perfused tissues, extracellular fluid, and blood with
rapid and uniform drug distribution.
 Peripheral compartments: composed of groups of tissues with lower blood perfusion and
different affinity for the drug with slow drug distribution.
• A drug will concentrate in a tissue in accordance with the affinity of the drug for that
particular tissue.

7. • There are several possible two-compartment models
Two-compartment open models, intravenous injection.

8. • The plasma level–time curve for a drug that follows a two-compartment model may be
divided into two parts,
(i) A distribution phase
(ii) An elimination phase.
• After an IV bolus injection, drug equilibrates rapidly in the central compartment.
• The distribution phase of the curve represents the initial, more rapid decline of drug
from the central compartment into the tissue compartment (line a).
• Although drug elimination and distribution occur concurrently during the distribution
phase, there is a net transfer of drug from the central compartment to the tissue
compartment.

9. • The fraction of drug in the tissue compartment is now in equilibrium (distribution
equilibrium) with the fraction of drug in the central compartment.
• The drug concentrations in both the central and tissue compartments decline in parallel and
more slowly compared to the distribution phase. This decline is a first-order process and is
called the elimination phase or the beta (β) phase ( line b).

10. • In the model depicted above, k 12 and k 21 are first- order rate constants that govern the
rate of drug change in and out of the tissues:
The relationship between the amount of drug in each compartment and the
concentration of drug in that compartment is shown by Equations
Where dp = amount of drug in the central compartment,
Dt = amount of drug in the tissue compartment,
Vp = volume of drug in the central compartment,
Vt = volume of drug in the tissue compartment.

11. METHOD OF RESIDUALS
• The method of residuals (also known as feathering, peeling, or curve stripping)
• For example, 100 mg of a drug was administered by rapid IV injection to a healthy 70-kg
adult male. Blood samples were taken periodically after the administration of drug, and the
plasma fraction of each sample w-as assayed for drug. The following data were obtained-

12. • The biexponential disposition curve obtained after i.v. bolus of a drug that fits two
compartment model can be resolved into its individual exponents by the method of residuals.
Plasma level–time curve for a two compartment open model.
The rate constants and intercepts were calculated by the method
of residuals.

13. Application of the method of residuals

14. Two-Compartment Open Model Extravascular Administration – First-Order Absorption
For a drug that enters the body by a first-order absorption process and distributed according
to two-compartment model, the rate of change in drug concentration in the central
compartment is described by 3 exponents —an absorption exponent, and the two usual
exponents

15. • The plasma concentration at any time t is given by equation:

16. Two-Compartment Open Model Intravenous Infusion
The plasma or central compartment concentration of a drug that fits two-compartment model when
administered as constant rate (zero-order) i.v. infusion, is given by equation:
At steady-state (i.e. at time infinity)

17. REFERENCES
• D.M.Brahmamkhar, Sunil.B.Jaiswal, Biopharmaceutics And Pharmacokinetics : A
Treatise, 212-272
• Shargel Leon, Andrew Yu B.C., “Applied biopharmaceutics and
pharmacokinetics” , 5 th edition, published by Mc Graw Hill ,page no. 185
.207,613-625.