Chemistry Reference
In-Depth Information
Ionisation of drugs
When a weakly acidic or basic drug is administered to the body, the drug
will ionise to a greater or lesser extent depending on its p
K
a
and the pH of
the body fluid in which it is dissolved. The pH of the body varies widely, but
the most important biological solution is the blood, which, as stated above,
normally has a pH of 7.4. An equation can be derived that will predict the
extent to which the drug ionises, and, as is often the case, the starting point
for the derivation is the Henderson-Hasselbalch equation (1.7).
[SALT]
pH
p
K
a
log —----
[ACID]
[A
]
pH
p
K
a
log —--
[HA]
Rearranging,
[HA]
p
K
a
pH
log —--
[A
]
and, therefore,
[HA]
[A
]
antilog(p
K
a
pH)
The fraction of the total drug that is ionised is given by
[A
]
—————-
[HA]
[A
]
so that the fraction ionised is
[A
]
—————————————---
[A
]
antilog(p
K
a
pH)
[A
]
which simplifies to
1
Fraction ionised
——————-------
1
antilog(p
K
a
pH)
(1.8)
Equation (1.8) applies to drugs that are weak acids and allows the fraction
of the total dose that is ionised to be calculated for any pH if the p
K
a
of the
drug is known. The equation is sometimes written as the percentage
ionised, which is simply given by
