Drug distribution between the central and peripheral compartments during multiple drug administration.

During multiple administration, the drug is accumulated in the central and the peripheral compartments until a steady state is achieved. At steady state the ratio of the amount of the drug in the peripheral compartment (Y) to the amount of the drug in the central compartment (X) will be constant.

(Y) Peripheral
compartment

k21

k12

(X) Central
compartment

k10

At steady state:

The rate of drug transfer from the central to the peripheral compartment is: k12 X

The rate of drug transfer from the peripheral to the central compartment is: k21 Y

Where X and Y are the amount of the drug in the central and peripheral compartments, respectively.

Since at steady state, the rate of drug transfer between the two compartments is similar :

k12 X = k21 Y

At steady state

Amount of the drug in the peripheral compartment (Y)

Amount of the drug in the central compartment (X)
=

k12

k21