PRINCIPLES OF TOXICOLOGY

The pK a is the negative logarithm of the acid dissociation constant. If, for example, the acid dissociation
constant K a is 10 –3 , then the pK a is 3.
The degree of ionization in body fluids depends on the pH of the medium as well as on the pK a of
the acid or base. This relationship can be expressed by the Henderson–Hasselbalch equations:
For acids:
For bases:
pKa − pH = log
pKa − pH = log
2.2 TRANSFER ACROSS MEMBRANE BARRIERS 39
Figure 2.2 Dependence of the ratio of permeability coefficient to partition coefficient on the cylindrical radius
of the diffusing molecule for diffusion of a series of lipophilic amides across the human red cell membrane. The
ordinate scale is in relative, not absolute, values. (P—propionamide; B—butyramide; IB—isobutyramide; V—
valeramide; IV—isovaleramide). The partition coefficients are P—0.01; B,IB—0.05; and V,IV—0.175. [Data from
Sha’afi et al. (1971).]
(nonionized form)
(ionized form)
= log (HA)
(A − )
(ionized form)
(nonionized form) = log (HB+ )
(B)
When the pH is equal to the pK a , half of the acid or base is present in the ionized form and half in the
nonionized form. At pH values less than the pK a , acids are less completely ionized. At pH greater than
the pK a , bases are less completely ionized. Another way of stating these relationships is that at a given