An ester group can be introduced into a local anesthetic, such as tolycaine (3.26),
to prevent the drug from reaching the CNS if it is injected intravascularly by accident
or abuse. The ester group is fairly stable in the tissues but is very rapidly hydrolyzed
in the serum to the polar carboxylic acid, which cannot penetrate the blood–brain
barrier.
3.5.3.2 Interference with Transport Characteristics
Interference with transport characteristics can serve many purposes. The introduction of
a hydrophilic “disposable moiety” can restrict a drug to the gastrointestinal tract and
prevent its absorption. Such a type of drug is represented by the intestinal disinfectant
succinyl-sulfathiazole (3.27). On the other hand, lipophilic groups can ensure peroral
activity, as in the case of the penicillin derivative pivampicillin (3.28), which enters the
circulation and then slowly releases the antibiotic in its free acid form, producing high
blood levels of the latter.
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