Kinetics of Drug Absorption

Most routes of drug administration depend upon the drug dissolving into body fluids and diffusing through one or more membranes to enter the blood plasma.  Therefore, all routes of administration, except intravenous, are classified as extravascular routes.  Drug absorption is defined as the appearance of the drug in plasma.

Oral administration is the most common extravascular route.  Administration of this form, either by solution or by rapidly dissolving solids (i.e. pills) often obey first-order kinetics.  Absorption is characterized by evaluating the absorption rate constant ka from plasma concentration versus time data graphs.

A kinetic model of first-order absorption is written:


DG = drug at the absorption site (gut)

DB = drug in the body

DE = eliminated drug

ka = first-order absorption rate constant

kel = overall elimination rate constant

The differential equations describing the rates of change of the three components DG, DB and DE are:

(1)     dDG/dt = -kaDG

(2)     dDB/dt = kaDG - kelDB

(3)     dDE/dt = +kelDB

Integrating Eq.1 we get

DG =DGOexp(-kat)

where DGO is the initial amount of drug presented to the absorbing region of the gut.  The DGO is equal to the dosage administered if the absorption is complete.

By substitution, we obtain

dDB/dt = +kaDGOexp(-kat)-kelDB

Using Laplace transforms, our equation becomes

where [(DGOka)/(ka-kel)] represents the amount of drug in the body through extravascular administration.  The two exponential terms represent elimination[exp(-kelt)] and absorption[exp(-kat)] of the drug.  By dividing both sides by Vd which is the apparent volume of distribution, we obtain the concentration of the drug within plasma versus time.