However, terfenadine was discovered to be the prodrug of the active molecule, fexofenadine, which does not carry the same risks as the parent compound.Therefore, fexofenadine could be placed on the market as a safe replacement for the original drug.Second generation antihistamines are less likely to cause impairment of cognitive facilities or performance skills.
Type IB agents rely on metabolic enzymes, especially in hepatic cells, to bioactivate the prodrugs intracellularly to active drugs.
Both major types can be further categorized into subtypes, based on factors such as (Type I) whether the intracellular bioactivation location is also the site of therapeutic action, or (Type 2) whether or not bioactivation occurs in the gastrointestinal fluids or in the circulation system.
See Table 1 below for further subtype categorization.
Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone.
For example, salicin is a β-D-glucopyranoside that is cleaved by esterases to release salicylic acid.