Seite - (000221) - in Biomedical Chemistry: Current Trends and Developments

efficient option to improve the oral bioavailability by utilizing amino acid transporters. Therefore, there are several other L-valyl ester prodrugs, including nucleoside analogues levovirin valinate, valopicitabine, and valtorcitabine currently undergoing clinical evaluation. L-Valyl ester prodrugs are probably the first commercial examples of amino acid prodrugs that utilize intestinal transporters to increase the permeability and consequently poor oral bioavailability of their parent drugs. Valacyclovir (Valtrex®) was the pioneer of L-valyl ester prodrugs, which achieved 3-5-times higher oral bioavailability (> 60%) (Soul- Lawton, 1995) than that of its parent drug, acyclovir (10−20%) (de Miranda and Blum, 1983). Valacyclovir is absorbed by the PepT1 and ATB0,+ transporters and is then rapidly hydrolyzed to acyclovir, predominantly by biphenyl hydrolase-like protein (valacyclovirase) (Kim, 2003; Hatanaka, 2004). Finally, acyclovir triphosphate acts as an antiherpetic agent by inhibiting viral DNA replication. Soon, after the discovery of valacyclovir, valganciclovir (Valcyte®) was designed. Valganciclovir is also absorbed by the PepT1 and ATB0,+ transporters then bioactivated by valacyclovirase (Kim, 2003; Umapathy, 2004). The oral bioavailability of ganciclovir is approximately 60%, which is almost 10-times higher than that from oral ganciclovir (6−8%) (Jung & Dorr, 1999).