Case Study: Valganciclovir: A Prodrug of Ganciclovir

Abstract

Valganciclovir (Valcyte™) is the commercially successful example of a number of prodrugs investigated to improve the oral bioavailability of ganciclovir (Cytovene ® ), a potent antiviral agent for the treatment of cytomegalovirus (CMV) infections ( Markham and Faulds, 1994 ). Ganciclovir is a fairly polar compound (logP = −1.65) limiting its uptake by passive routes and has moderate solubility in water at pH 7 (6 mg/mL at 37°C). Ganciclovir is supplied in two formulations: a) a intravenous formulation (IV) in the form of a lyophilized powder of the sodium salt to be reconstituted with water and b) a oral tablet formulation (Physician’s Desk Reference 2004). The IV formulation is quite basic and has to be administered slowly in dilute form. The oral formulation is adversely impacted by the physical properties of the compound, resulting in an oral bioavailability of approximately 7%. Therefore, the oral formulation is used mainly for maintenance therapy, while for induction therapy, IV formulations are being used to assure adequate exposure levels.