The occurrence of prodrugs among the world's 100 top-selling pharmaceuticals in 2009
| Prodrug Name (Trade Name) and Therapeutic Area | Functional Group | Prodrug Strategy |
|---|---|---|
| Proton pump inhibitors | ||
| Esomeprazole (Nexium) Lansoprazole (Prevacid) Pantoprazole (Protonix) Rabeprazole (Aciphex) | Formation of active sulfonamide form | Bioprecursor prodrugs that are converted into their respective active sulfonamide forms site-selectively in acidic conditions of stomach |
| Antiplatelet agent | ||
| Clopidogrel (Plavix) | Formation of the active thiol | Bioprecursor prodrug that selectively inhibits platelet aggregation |
| Antiviral agent | ||
| Valacyclovir (Valtrex) | l-Valyl ester of acyclovir | Bioconversion by valacyclovir hydrolase (valacyclovirase) |
| Transported predominantly by hPEPT1 | ||
| Oral bioavailability improved from 12–20% (acyclovir) to 54% (valacyclovir) | ||
| Hypercholesterolemia | ||
| Fenofibrate (Tricor) | Isopropyl ester of fenofibric acid | Lipophilic ester of fenofibric acid |
| Antiviral agent | ||
| Tenofovir disoproxil (Atripla) | Bis-(isopropyloxy-carbonyloxymethyl) ester of tenofovir | Bioconversion by esterases and phosphodiesterases |
| The oral bioavailability of tenofovir from tenofovir disoproxil is 39% after food | ||
| Psychostimulant | ||
| Lisdexamfetamine (Vyvanse) | l-Lysyl amide of dextroamphetamine | Bioconversion by intestinal or hepatic hydrolases |
| Reduced potential for abuse due to prolonged release of active drug | ||
| Influenza | ||
| Oseltamivir (Tamiflu) | Ethyl ester of oseltamivir carboxylate | Improved bioavailability compared with oseltamivir carboxylate, allowing oral administration |
| Hypertension | ||
| Olmesartan medoxomil (Benicar) | Cyclic carbonate ester of olmesartan | Improved bioavailability compared with olmesartan, allowing oral administration |
| Immunosuppressant | ||
| Mycophenolate mofetil (CellCept) | Morpholinyl ethyl ester of mycophenolic acid | Improved oral bioavailability with less variability |
| Glaucoma | ||
| Latanoprost (Xalatan) | Isopropyl ester of latanoprost acid | Bioconversion by esterases |
| Improved lipophilicity to achieve better ocular absorption and safety |