Kinetic Process of Drug Absorption: Understanding Compartment Models

Topics: Pharmacokinetics, Pharmacology Pages: 8 (688 words) Published: September 26, 2015
Compartment Model:
Compartment Models are the classical pharmacokinetic models that simulate the kinetic process of drug absorption, distribution and elimination with little physiological details. Two Compartment Open Model:

A drug that follows the pharmacokinetics of a two compartment model does not rapidly equilibrate throughout the body as is assumed for a one-compartment model. In this model there are two compartments and the drug distributes itself into these two compartments. Central Compartment:

Blood, extracellular fluid, and highly perfused tissues.
The drug distributes rapidly and uniformly in Central Compartment. Tissue or Peripheral Compartment:
Tissue in which drug equilibrates more slowly.
Drug transfer between the two compartments is assumed to take place by First-order processes.

The model A is most used. The rate constants k12 and K21 represent the first order rate transfer constants for movement of drug from compartment 1 to compartment 2 (k12) and from compartment 2 to compartment 1 (k21). These are microconstants and their values cannot be estimated directly. Mostly it is assumed that elimination occurs from the central compartment model (model A), because the major sites of drug elimination occur in organs, such as kidney and liver which are highly perfused with blood. Plasma Level-time curve:

For the drugs which follow two-compartment model may be divided into two part: A distribution phase
Elimination phase
After I.V bolus of a drug the decline in the plasma conc. Is biexponential.

Drug Concentration in Central Compartment:
There is a net transfer of drug from the central compartment to the tissue compartment. The fraction of drug in the tissue compartment during the distribution phase increases up to a maximum. This model assumes that, at t=0 no drug is in the tissue compartment. After I.V administration the drug is rapidly transferred to the tissue and the blood level of drug is also declined due to elimination and due to the transfer from Central compartment to other tissues. Above figure shows a single I.V dose. The rate of change in drug conc. In the central compartment is given as: dCc/dt= k21Cp – k12Cc - KECC (1) Cc= Drug concentration in central compartment Cp= Drug concentration in peripheral compartment k12= First order distribution rate constant from liver to libra k21= First oreder distrubution of constatn from peripheral to KE= Elimination rate constant from Central Compartment Extending the relationship X=VdC

X= the amount of drug in the body at any time t remaining to be eliminate. C= Drug concentration in Plasma.
Vd= proportionality constant apparent volume of distribution.
where,
Xc= amount of drug C1
Xp= amount of drug C2
Vc and Vp = apparent volume of drug C1 and C2
Drug Concentration in Tissue compartment:
It can be calculated once the parameters for the model are determined. However it is the average drug concentration in the tissue compartments. Real tissue drug concentration can sometimes be calculated by addition of compartments to the model until experimental tissue mimicking compartment is found. Although the nature of tissue compartment is hypothetical but theoretical tissue level is still valuable to clinicians. The rate of change of drug concentration in the peripheral component is given by: dCp/dt= k12Cc - k21Cp (3)

=k12Xc/Vc – K21­Xp/ Vp (4) Integration of above equation (3) and (4) gives the concentration of drug In central and peripheral compartment at any given time t: Cc=Xo/Vc [( K21 – α/β-α)e-αt + (K21 – β/β-α)e-βt ] (5)...
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