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DISTRIBUTION PHASE AND ELIMINATION PHASE

Definition

Distribution phase: During the distribution phase, changes in the concentration of drug in plasma reflect primarily movement of drug within, rather than loss from, the body.

Elimination phase (late phase): Once the drug in the plasma and tissues has reached equilibrium, the decline of plasma concentration is driven by elimination of the drug from the body.

Time course of the plasma concentration of a drug applied by a single i.v. injection.

Description

These two distinct phases in the plasma concentration versus time plot are described in the figure.

The figure shows drug plasma concentrations after intravenous injection as a semi-logarithmic plot. Two different phases can be distinguished, an initial phase during which the plasma concentration steeply decreases, and a second, linear phase, which is less steep. Directly after injection, the drug is mainly present in the plasma volume. Very rapidly, it distributes into the different tissues. The initial steep phase of the curve is called distribution phase because distribution into tissues primarily determines the early rapid decline in plasma concentration.  With time, distribution equilibrium of drug in tissue with that in plasma is established in more and more tissues, and finally (during the linear phase in the semi-logarithmic plot) changes in plasma concentration reflect a proportional change in the concentrations of drug in all tissues and therefore in the amount of drug in the body. During this proportionality phase, the body acts kinetically as a single compartment. During this phase, the decline of the plasma concentration is associated solely with elimination of drug from the body, in other words it corresponds to the kinetics of drug elimination. Therefore,  this phase is often called the elimination phase. Parameters associated with it, such as the elimination rate constant and the elimination half-life (t1/2) can be estimated from the terminal slope of the plasma concentration – time profile.

 

Definition and importance of C(0):

C(0) = back-extrapolated plasma drug concentration at time zero following bolus intravenous injection. It corresponds to the plasma concentration of the drug directly after injection, if distribution was immediate. C(0) can be determined from the graph by extrapolating the fit to the elimination phase back to t=0. C(0) is used to determine the apparent volume of distribution.

It is important to note that C(0) does not correspond to the maximal drug concentration in plasma.