The rate constant, ka, is the natural log of the proportion of the xenobiotic that
has been absorbed in one unit of time. If half of the xenobiotic is absorbed in
one hour, the concentration at the site of absorption will have decreased by a
factor of 2; in this case, ka is ln 2 ÷ 1 hr, or 0.693/hr.
Therefore, ka = (0.693) ÷ t½ .
For example, the concentration of an ingested toxicant in the stomach
determines, for the most part, the rate at which the toxicant is absorbed from
the stomach into the blood; as the concentration of the toxicant in the stomach
decreases due to absorption into the blood, the rate at which more toxicant is
absorbed also decreases.
For most toxicants at high dose, the concentration of the xenobiotic at the site
of absorption may be so high that the amount being absorbed per unit time has
little effect on the concentration at time t, Ct. The rate of absorption will be
independent of Ct until the concentration decreases to a much lower value.
Under these conditions, the rate of absorption is constant and follows zeroorder
kinetics. Figure 6 compares the rate of absorption of a xenobiotic
under two conditions of zero-order and first-order kinetics, plotting the data as
a linear function of the plasma concentration of the xenobiotic. Figure 7 takes
the same data and plots the plasma concentration as a log function.
Figure 6. Rate of absorption from blood, linear plot