Most drugs are either weak acids or base
--> Exist in 2 forms in solution
When pH = pK
--> Ionised fraction = non-ionised fraction
More ionised at alkaline pH (high pH)
e.g. barbituates
More ionised at acidic pH (low pH)
e.g. opioids, local anaesthetics
Non-ionised fraction
--> High lipid solubility
--> Equilibrate across cell membrane
When pH differs across cell membranes
--> Total drug level across the membrane will differ
For example,
Non-ionised weak basic drug diffuses into stomach
--> Low pH causes the drug to become ionised
Thus,
Weak base accumulates in stomach
Similarly,
Local anaesthetics (weak base) accumulates in foetus (lower pH)