Ganciclovir and Valganciclovir Use in Children

Marcia L. Buck, Pharm.D., FCCP, FPPAG

Disclosures

Pediatr Pharm. 2009;15(10) 

In This Article

Mechanism of Action

Ganciclovir is a synthetic acyclic nucleoside analogue of 2'-deoxyguanosine. Valganciclovir is the L-valyl ester of ganciclovir. After oral administration, it is rapidly cleaved by esterases in the intestine wall and liver to form active ganciclovir. Ganciclovir inhibits replication of herpes viruses, including CMV and herpes simplex virus (HSV). In CMV-infected cells, ganciclovir undergoes phosphorylation to a monophosphate form by a CMV-encoded (UL97 gene) protein kinase. Significantly greater phosphorylation occurs in CMV-infected cells than in non-infected cells. Ganciclovir monophosphate is then converted to diphosphate and triphosphate forms by cellular kinases.[1–4]

Ganciclovir triphosphate, the active moiety, persists for several days in CMV-infected cells. It inhibits viral DNA synthesis by competing with deoxyguanosine triphosphate as a substrate for viral DNA polymerase. Ganciclovir triphosphate is also incorporated into viral DNA, resulting in termination of viral DNA elongation and inhibition of viral replication. The in vitro median concentration of ganciclovir that inhibits CMV replication ranges from 0.1 to 3.48 mcg/mL. Viral resistance to ganciclovir has been demonstrated in vitro and in vivo, with treatment failures reported in patients on long-term therapy for CMV retinitis. After prolonged administration, selection of mutations in UL97 or in the viral polymerase gene UL54 results in a reduced formation of ganciclovir triphosphate.[1–4]

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