USING pK a VALUES
165
• Very weak acids with pK a values greater than 7.5
will be essentially non-ionized at all pH values in
the range 1–8, so that absorption will be largely
independent of pH.
• Acids with pK a values in the range 2.5–7.5 will
be characterized by significant changes in the
proportion of non-ionized drug according to the
pH. As the pH rises, the percentage of nonionized drug decreases, and absorption therefore
also decreases.
• Absorption of stronger acids (pK a less than about
2.5) should also depend upon pH, but the fraction
that is non-ionized is going to be very low except
under the most acidic conditions in the stomach.
Absorption is typically low, even under acidic
conditions.
• Basic drugs will not be absorbed from the stomach,
where the pH is strongly acidic.
• Excretion of drugs will be affected by the pH
of the urine. If the urine is acidic, weak bases
are ionized and there will be poor re-absorption.
With basic urine, weak bases are non-ionized
and there is more re-absorption. The pH of the
urine can be artificially changed in the range
5–8.5: oral administration of sodium bicarbonate
(NaHCO 3 ) increases pH values, whereas ammonium chloride (NH 4 Cl) lowers them. Thus, urinary acidification will accelerate the excretion of
weak bases and retard the excretion of weak
acids. Making the urine alkaline will facilitate the
excretion of weak acids and retard that of weak
bases.
165
• Very weak acids with pK a values greater than 7.5
will be essentially non-ionized at all pH values in
the range 1–8, so that absorption will be largely
independent of pH.
• Acids with pK a values in the range 2.5–7.5 will
be characterized by significant changes in the
proportion of non-ionized drug according to the
pH. As the pH rises, the percentage of nonionized drug decreases, and absorption therefore
also decreases.
• Absorption of stronger acids (pK a less than about
2.5) should also depend upon pH, but the fraction
that is non-ionized is going to be very low except
under the most acidic conditions in the stomach.
Absorption is typically low, even under acidic
conditions.
• Basic drugs will not be absorbed from the stomach,
where the pH is strongly acidic.
• Excretion of drugs will be affected by the pH
of the urine. If the urine is acidic, weak bases
are ionized and there will be poor re-absorption.
With basic urine, weak bases are non-ionized
and there is more re-absorption. The pH of the
urine can be artificially changed in the range
5–8.5: oral administration of sodium bicarbonate
(NaHCO 3 ) increases pH values, whereas ammonium chloride (NH 4 Cl) lowers them. Thus, urinary acidification will accelerate the excretion of
weak bases and retard the excretion of weak
acids. Making the urine alkaline will facilitate the
excretion of weak acids and retard that of weak
bases.