Activation of Prodrugs Depend on the Metabolism of These Prodrugs

Prodrugs depend on enzymatic processes, essentially in the liver, but can also occur in other tissues to release the active metabolite. These metabolic biotransformations are often enzymatically controlled, ensuring the drug becomes pharmacologically active at its site of action. Metabolism may occur at the target site (e.g., in viruses, where drugs are phosphorylated) or in the liver or other tissues. For example, codeine is activated by demethylation to morphine, which is a more active analgesic than codeine. Clopidogrel oxidized to 2-oxoclopidogrel which is active and 2-oxoclopidogrel which is metabolized in two active thiol metabolite. Enalapril is a prodrug that is metabolized to enalaprilat, the active form. L-Dopa is a prodrug that is converted into dopamine in the brain by decarboxylation. Azathioprine is metabolized to mercaptopurine, which is immunosuppressive. Sulfasalazine is a prodrug metabolized by azoreductase and converted to 5-aminosalicylic acid and sulfapyridine, which are more active than sulfasalazine. Prontosil is a prodrug converted into sulfanilamide, which is more active than prontosil. Salicin is a glycoside that is metabolized into salicylic acid, which is active as an analgesic. Valacyclovir is metabolized into acyclovir, which is an active antiviral.