Medicinal Chemistry

p-acetaminophenol. Another classical example of side-effect masking occurs in aspirin
(3.34) and its many analogs — the result of a considerable effort to eliminate the gastric
bleeding caused by salicylic acid.
Selective bioactivation (toxification) is illustrated in the case of the insecticide
malathion (3.35). This acetylcholinesterase inhibitor is desulfurized selectively to the
toxic malaoxon, but only by insect and not mammalian enzymes. Malathion is therefore
relatively nontoxic to mammals (LD 50 =1500 mg/kg, rat; p.o.). Higher organisms
rapidly detoxify malathion by hydrolyzing one of its ester groups to the inactive acid, a
process not readily available to insects. This makes the compound doubly toxic to
insects since they cannot eliminate the active metabolite.

3.5.3.4 Improvement of Taste

Taste improvement is quite an important aspect of drug modification, especially in pedi-
atric medicine. The extremely bitter taste of some antibiotics, such as clindamycin (3.36)
or chloramphenicol (3.37), can be masked successfully by preparing esters or pamoate
salts of these drugs, which are very insoluble and therefore have no taste.

3.5.4 Innovations in Drug Delivery

Novel drug delivery systems can also have a profound effect on pharmacokinetics, even
if they do not involve the use of prodrugs in the classical sense. Novel polymers have
permitted the development of membranes with controlled diffusion rates. For example,

158 MEDICINAL CHEMISTRY