Barrier to Overcome | Examples of Applicable Prodrugs | Preferable Site of Bioconversion | Common Functional Groups Amenable to the Prodrug Method |
---|---|---|---|
Formulation and administration | Introducing ionizable or polar neutral group | During or after absorption | -OH -SH -NH (via spacer) -COOH |
|
|
| |
Absorption | Masking polar ionized/non-ionized group(s) | After absorption | -OH -SH -NH -COOH -OPO(OH)2 |
|
|
| |
Distribution | Targeting cell- or tissue-specific transporters or enzymes | In the target tissue | -OH -SH -NH -COOH |
|
|
| |
Metabolism and excretion | Masking metabolically labile group(s) or polar ionized/nonionized group(s) | After absorption | -OH -SH -NH -COOH -OPO(OH)2 |
|
|
| |
Toxicity | Targeting tissue-specific enzymes or divergent conditions of target tissue | In the target tissue | Depending on the selected prodrug method (these prodrugs are often bioprecursors) |
|
|
| |
Life-cycle management | Introducing any kind of promoiety | Depending on the selected prodrug method | Depending on the selected prodrug method (these prodrugs are often carrier-linked prodrugs) |
|
GI, gastrointestinal.